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Form 8-K

sec.gov

8-K — CASTLE BIOSCIENCES INC

Accession: 0001628280-26-031255

Filed: 2026-05-06

Period: 2026-05-06

CIK: 0001447362

SIC: 8071 (SERVICES-MEDICAL LABORATORIES)

Item: Results of Operations and Financial Condition

Item: Regulation FD Disclosure

Item: Financial Statements and Exhibits

Documents

8-K — cstl-20260506.htm (Primary)

EX-99.1 (exhibit991q12026earningsre.htm)

EX-99.2 (exhibit992q12026.htm)

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8-K

8-K (Primary)

Filename: cstl-20260506.htm · Sequence: 1

cstl-20260506

0001447362FALSE00014473622026-05-062026-05-06

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): May 6, 2026

Castle Biosciences, Inc.

(Exact name of registrant as specified in its charter)

Delaware   001-38984   77-0701774

(state or other jurisdiction

of incorporation)   (Commission

File Number)   (I.R.S. Employer

Identification No.)

1500 W. Parkwood Ave, Suite 400

Friendswood, Texas

77546

(Address of principal executive offices) (Zip Code)

Registrant’s telephone number, including area code: (866) 788-9007

(Former name or former address, if changed since last report.)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐    Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐    Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐    Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐    Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class Trading Symbol(s)   Name of each exchange on which registered

Common Stock, $0.001 par value per share CSTL   The Nasdaq Global Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b–2 of the Securities Exchange Act of 1934 (§ 240.12b–2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Item 2.02    Results of Operations and Financial Condition.

On May 6, 2026, Castle Biosciences, Inc. (the “Company”) issued a press release announcing its financial results for the first quarter ended March 31, 2026. A copy of the press release is attached hereto as Exhibit 99.1 and incorporated herein by reference.

The information contained or incorporated in this Current Report on Form 8-K, including Exhibit 99.1, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed to be incorporated by reference into any filing under the Exchange Act or the Securities Act of 1933, as amended (the “Securities Act”), except as expressly set forth by specific reference in such filing to this Current Report on Form 8-K.

Item 7.01    Regulation FD Disclosure.

On May 6, 2026, the Company made available the slide presentation attached hereto as Exhibit 99.2. Information from this slide presentation may also be used by the management of the Company in future meetings regarding the Company.

The information contained or incorporated in this Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.2, shall not be deemed “filed” for purposes of Section 18 of the Exchange Act or otherwise subject to the liabilities of that section, nor shall it be deemed to be incorporated by reference into any filing under the Exchange Act or the Securities Act except as expressly set forth by specific reference in such filing to this Current Report on Form 8-K.

Item 9.01    Financial Statements and Exhibits.

(d) Exhibits.

Exhibit

Number Description

99.1

Press release issued May 6, 2026.

99.2

Slide presentation.

104 Inline XBRL for the cover page of this Current Report on Form 8-K.

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

CASTLE BIOSCIENCES, INC.

By: /s/ Frank Stokes

Frank Stokes

Chief Financial Officer

Date: May 6, 2026

EX-99.1

EX-99.1

Filename: exhibit991q12026earningsre.htm · Sequence: 2

Document

Exhibit 99.1

Castle Biosciences Reports First Quarter 2026 Results

Delivered Q1 2026 revenue of $83.7 million

Q1 2026 total test reports for our core revenue drivers (DecisionDx®-Melanoma, TissueCypher®) increased 36% over Q1 2025

Raising full-year 2026 revenue guidance to $345-355 million from $340-350 million

Conference call and webcast today at 4:30 p.m. ET

FRIENDSWOOD, Texas – May 6, 2026 – Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, today announced its financial results for the first quarter ended March 31, 2026.

“The Castle Biosciences team delivered outstanding results to start 2026, delivering $83.7 million in revenue,” said Derek Maetzold, president and chief executive officer of Castle Biosciences. “I thank our team for their dedication and focus, which translates directly to our performance. Our momentum this quarter reflects our robust execution and the strength of our core revenue drivers, with both DecisionDx-Melanoma and TissueCypher achieving double digit year-over-year test volume growth, 16% and 58%, respectively. As a result of our first quarter performance and continued confidence in the business, we are raising our 2026 total revenue guidance to $345-355 million, compared to the previously provided guidance of $340-350 million.

“In addition, during the quarter we expanded the body of evidence supporting our market-leading DecisionDx-Melanoma test. Specifically, we announced new data from a prospective, multicenter, U.S. based study demonstrating that patients with a less than 5% predicted risk of sentinel lymph node positivity had an actual positivity rate of just 2.6%, reinforcing DecisionDx-Melanoma’s ability to guide sentinel lymph node biopsy decision-making in line with guideline thresholds. Our substantial body of evidence is a key driver of adoption and an important differentiator for DecisionDx-Melanoma and our innovative test portfolio more broadly, reinforcing our position of strength as we continue to execute across the business.”

First Quarter Ended Mar. 31, 2026, Financial and Operational Highlights

•Revenues were $83.7 million, compared to $88.0 million in the first quarter of 2025. Affecting first quarter 2026 revenue was the change in DecisionDx-SCC Medicare coverage effective April 24, 2025, the re-focus of our commercial efforts, as well as the discontinuation of IDgenetix in May 2025.

◦Revenues for our non-dermatologic tests were $42.6 million, compared to $25.0 million during the same period in 2025.

Core revenue drivers:

•First quarter 2026 total test reports for our core revenue drivers (DecisionDx-Melanoma, TissueCypher) increased 36% over the first quarter of 2025:

◦DecisionDx-Melanoma test reports delivered in the quarter were 10,021, compared to 8,621 in the first quarter of 2025.

◦TissueCypher Barrett’s Esophagus test reports delivered in the quarter were 11,745, compared to 7,432 in the first quarter of 2025.

Additional tests:

◦DecisionDx-SCC test reports delivered in the quarter were 3,702, compared to 4,375 in the first quarter of 2025.

◦MyPath® Melanoma test reports delivered in the quarter were 973, compared to 926 in the first quarter of 2025.

◦DecisionDx®-UM test reports delivered in the quarter were 492, compared to 470 in the first quarter of 2025.

•Gross margin was 73%, and Adjusted Gross Margin was 76%, compared to 49% and 81%, respectively, for the same periods in 2025. Affecting first quarter 2025 gross margin was the one-time adjustment of an acceleration of amortization expense of approximately $20.1 million.

•Net cash used in operations was $22.1 million, compared to net cash used in operations of $6.0 million for the same period in 2025. First quarter 2026 cash use reflects payout of employee annual cash bonuses as well as certain health care benefit payments, totaling $28.8 million, that are not expected to recur during the remainder of 2026.

•Net loss, which includes non-cash stock-based compensation expense of $9.8 million, was $14.5 million, compared to net loss of $25.8 million for the same period in 2025.

•Net loss per share, Basic and Diluted, was $0.49, compared to net loss per share, Basic and Diluted of $0.90 and Adjusted Net Loss per Share, Basic and Diluted, of $0.20, for the same period in 2025.

•Adjusted EBITDA was $(5.1) million, compared to $13.0 million for the same period in 2025.

Cash, Cash Equivalents and Marketable Investment Securities

As of Mar. 31, 2026, the Company’s cash, cash equivalents and marketable investment securities totaled $261.7 million.

2026 Outlook

Castle Biosciences is raising its guidance for anticipated total revenue in 2026. The Company now anticipates generating between $345-355 million in total revenue in 2026, compared to the previously provided guidance of between $340-350 million.

First Quarter and Recent Accomplishments and Highlights

Dermatology - Skin Cancer

•The Company presented new data at the 2026 American Academy of Dermatology Annual Meeting demonstrating that its DecisionDx-Melanoma test refines mortality risk within American Joint Committee on Cancer (AJCC) stages for patients with cutaneous melanoma (CM). The data showed that DecisionDx-Melanoma identifies clinically meaningful differences in mortality risk among patients within the same stage, which may help clinicians more confidently escalate care for higher-risk patients while avoiding unnecessary interventions in those at lower risk of poor outcomes. See the Company’s news release from March 27, 2026, for more information.

•The Company also announced new data from a prospective, multicenter study evaluating DecisionDx-Melanoma’s integrated sentinel lymph node biopsy (i31-SLNB) test result. The study data confirmed that the i31-SLNB accurately predicts SLN positivity and identifies low-risk patients who may safely consider forgoing SLNB while maintaining favorable long-term outcomes. These results expanded upon earlier publications from the same prospective, multicenter clinical study and further strengthened the growing body of evidence supporting the role of DecisionDx-Melanoma in guiding SLNB decision-making. The paper, available in Future Oncology, confirmed that DecisionDx-Melanoma’s i31-SLNB identifies patients below the 5% National Comprehensive Cancer Network® (NCCN) threshold for forgoing sentinel lymph node biopsy and outperforms traditional staging

criteria and other predictive gene expression profile (GEP) tests. See the Company’s news release from March 9, 2026, for more information.

•The Company presented new data at the European Congress of Dermato-Oncology (EADO) Congress and the American College of Mohs Surgery (ACMS) Annual Meeting demonstrating that its DecisionDx-Melanoma test provides independent, personalized prognostic information beyond AJCC staging, identifying biologically high-risk patients—including those with thin and early-stage disease—and supporting more precise, risk-aligned clinical management. See the Company’s news release from April 21, 2026, for more information.

•The Company is supporting a series of initiatives across the country during May in recognition of Skin Cancer Awareness Month, including advocacy walks, community skin cancer screenings and patient education programs in collaboration with leading patient advocacy organizations. These efforts are aimed at expanding access to early detection, education and community-based resources to help prevent skin cancer and improve patient outcomes. See the Company’s news release from May 5, 2026, for more information.

Gastroenterology

•The Company announced that new data from Mayo Clinic researchers, presented at Digestive Disease Week®, demonstrate that its TissueCypher test improves risk stratification and informs real-world management decisions for patients with Barrett’s esophagus, including influencing surveillance intervals in more than half of patients and enabling more personalized, risk-aligned care. See the Company’s news release from May 4, 2026, for more information.

Dermatology - Atopic Dermatitis

•The Company announced the publication of a prospective, multicenter clinical validation study in the Journal of the American Academy of Dermatology (JAAD) demonstrating that its AdvanceAD-Tx test can identify patients with moderate-to-severe atopic dermatitis who are significantly more likely to achieve greater and faster clinical responses when treated with a Janus kinase inhibitor compared to T helper type 2-targeted therapies. See the Company’s news release from February 19, 2026, for more information.

Conference Call and Webcast Details

Castle Biosciences will hold a conference call on Wednesday, May 6, 2026, at 4:30 p.m. Eastern time to discuss its first quarter 2026 results and provide a corporate update.

A live webcast of the conference call can be accessed here: https://events.q4inc.com/attendee/621816679 or via the webcast link on the Investor Relations page of the Company’s website, https://ir.castlebiosciences.com/overview/default.aspx. Please access the webcast at least 10 minutes before the conference call start time. An archive of the webcast will be available on the Company’s website until May 27, 2026.

There will be a brief Question & Answer session following management commentary.

Use of Non-GAAP Financial Measures (UNAUDITED)

In this release, we use the metrics of Adjusted Revenues, Adjusted Gross Margin, Adjusted EBITDA and Adjusted Net Loss per Share, Basic and Diluted, which are non-GAAP financial measures and are not calculated in accordance with generally accepted accounting principles in the United States (GAAP). Adjusted Revenues and Adjusted Gross Margin reflect adjustments to GAAP net revenues to exclude net positive and/or net negative revenue adjustments recorded in the current period associated with changes in estimated variable consideration related to test reports delivered in previous periods. Adjusted Gross Margin further excludes acquisition-related intangible asset amortization. Adjusted EBITDA excludes from net loss: interest income, interest expense, income tax benefit or expense, depreciation and amortization expense, stock-based compensation expense and net (gains) losses on equity securities. Adjusted Net Loss per Share, Basic and Diluted, excludes a one-time adjustment of an acceleration of amortization expense for our IDgenetix test from net loss.

We use Adjusted Revenues, Adjusted Gross Margin, Adjusted EBITDA and Adjusted Net Loss per Share, Basic and Diluted, internally because we believe these metrics provide useful supplemental information in assessing our revenue and operating performance reported in accordance with GAAP, respectively. We believe that Adjusted Revenues, when used in conjunction with our test report volume information, facilitates investors’ analysis of our current-period revenue performance and average selling price performance by excluding the effects of revenue adjustments related to test reports delivered in prior periods, since these adjustments may not be indicative of the current or future performance of our business. We believe that providing Adjusted Revenues may also help facilitate comparisons to our historical periods. Adjusted Gross Margin is calculated using Adjusted Revenues and therefore excludes the impact of revenue adjustments related to test reports delivered in prior periods, which we believe is useful to investors as described above. We further exclude acquisition-related intangible asset amortization in the calculation of Adjusted Gross Margin. We believe that excluding acquisition-related intangible asset amortization may facilitate gross margin comparisons to historical periods and may be useful in assessing current-period performance without regard to the historical accounting valuations of intangible assets, which are applicable only to tests we acquired rather than internally developed. Adjusted Net Loss per Share, Basic and Diluted, is calculated by excluding a one-time adjustment of an acceleration of amortization expense for our IDgenetix test from net loss. We believe that providing Adjusted Net Loss per Share, Basic and Diluted, may also help facilitate comparisons to our historical periods. We believe Adjusted EBITDA may enhance an evaluation of our operating performance because it excludes the impact of prior decisions made about capital investment, financing, investing and certain expenses we believe are not indicative of our ongoing performance. However, these non-GAAP financial measures may be different from non-GAAP financial measures used by other companies, even when the same or similarly titled terms are used to identify such measures, limiting their usefulness for comparative purposes.

These non-GAAP financial measures are not meant to be considered in isolation or used as substitutes for net revenues, gross margin, net loss or net loss per share reported in accordance with GAAP; should be considered in conjunction with our financial information presented in accordance with GAAP; have no standardized meaning prescribed by GAAP; are unaudited; and are not prepared under any comprehensive set of accounting rules or principles. In addition, from time to time in the future, there may be other items that we may exclude for purposes of these non-GAAP financial measures, and we may in the future cease to exclude items that we have historically excluded for purposes of these non-GAAP financial measures. Likewise, we may determine to modify the nature of adjustments to arrive at these non-GAAP financial measures. Because of the non-standardized definitions of non-GAAP financial measures, the non-GAAP financial measure as used by us in this press release and the accompanying reconciliation tables have limits in their usefulness to investors and may be calculated differently from, and therefore may not be directly comparable to, similarly titled measures used by other companies. Accordingly, investors should not place undue reliance on non-GAAP financial measures. Reconciliations of these non-GAAP financial measures to the most directly comparable GAAP financial measures are presented in the tables at the end of this release.

About Castle Biosciences

Castle Biosciences (Nasdaq: CSTL) is a leading diagnostics company improving health through innovative tests that guide patient care. With a primary focus in dermatologic and gastroenterological disease, we develop personalized, clinically actionable solutions that help improve disease management and patient outcomes.

We put people first—empowering patients and clinicians and informing care decisions through rigorous science and advanced molecular tests that support more confident treatment planning. To learn more, visit www.CastleBiosciences.com and connect with us on LinkedIn, Facebook, X and Instagram.

DecisionDx-Melanoma, DecisionDx-CMSeq, i31-SLNB, i31-ROR, DecisionDx-SCC, MyPath Melanoma, AdvanceAD-Tx, TissueCypher, Esopredict, DecisionDx-UM, DecisionDx-PRAME and DecisionDx-UMSeq are trademarks of Castle Biosciences, Inc.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the “safe harbor” created by those sections. These forward-looking statements include, but are not limited to, statements concerning our expectations regarding: Castle’s 2026 total revenue guidance of $345-355 million; continued top-line performance and growth of test volumes; the ability of DecisionDx-Melanoma, DecisionDx-SCC, TissueCypher and AdvanceAD-Tx to bring substantial added value to clinicians and their patients; the ability of DecisionDx-Melanoma to (i) reduce mortality risk compared to untested patients, (ii) improve patient survival, (iii) provide clarity in overall risk beyond histology, and (iv) guide sentinel lymph node biopsy decision-making, including through the i31-SLNB test result, by accurately predicting SLN positivity and identifying low-risk patients who may safely consider forgoing SLNB; the ability of DecisionDx-SCC to (i) predict individual risk of metastasis, benefit from ART and risk of LR, (ii) provide comprehensive results to support tailored post-surgical management and treatment pathway recommendations and (iii) provide actionable decision points based on individual patient risk; the anticipated success of our launch of AdvanceAD-Tx; and Castle’s ability to achieve near- and long-term success and the continued growth of our portfolio. The words “anticipate,” “can,” “could,” “expect,” “goal,” “guidance,” “may,” “plan,” “potentially,” “providing,” “upcoming” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions, or expectations disclosed in our forward-looking statements and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. These forward-looking statements involve risks and uncertainties that could cause our actual results to differ materially from those in the forward-looking statements, including, without limitation: our assumptions or expectations regarding reimbursement for our products and subsequent coverage decisions; our estimated total addressable markets for our products and product candidates and the related expenses, capital requirements and potential needs for additional financing; the anticipated cost, timing and success of our product candidates; our plans to research, develop and commercialize new tests; our ability to successfully integrate new businesses, assets, products or technologies acquired through acquisitions; the effects of macroeconomic events and conditions, including inflation and monetary supply shifts, labor shortages, liquidity concerns at, and failures of, banks and other financial institutions or other disruptions in the banking system or financing markets, recession risks, supply chain disruptions, tariffs, outbreaks of contagious diseases and geopolitical events (such as the ongoing conflicts in the Middle East and Ukraine-Russia conflict), among others, on our business and our efforts to address any impact on our business; the possibility that subsequent study or trial results and findings may contradict earlier study or trial results and findings or may not support the results discussed in this press release, including with respect to the tests discussed in this press release; our planned installation of additional equipment and supporting technology infrastructures and implementation of certain process efficiencies may not enable us to increase the future scalability of our TissueCypher Test; the possibility that actual application of our tests may not provide the aforementioned benefits to patients; the possibility that our newer gastroenterology franchise may not contribute to the achievement of our long-term financial targets as anticipated; and the risks set forth under the heading “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2025 and our Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, each filed or to be filed with the SEC, and in our other filings with the SEC. The forward-looking statements are applicable only as of the date on which they are made, and we do not assume any obligation to update any forward-looking statements, except as may be required by law.

Investor Relations Contact:

Camilla Zuckero

czuckero@castlebiosciences.com

281-906-3868

Media Contact:

Allison Marshall

amarshall@castlebiosciences.com

###

CASTLE BIOSCIENCES, INC.

CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS

(UNAUDITED)

(in thousands, except per share data)

Three Months Ended

March 31,

2026 2025

NET REVENUES $ 83,679  $ 87,988

OPERATING EXPENSES

Cost of sales (exclusive of amortization of acquired intangible assets) 20,533  16,383

Research and development 14,428  12,588

Selling, general and administrative 64,899  58,620

Amortization of acquired intangible assets 2,226  28,325

Total operating expenses, net 102,086  115,916

Operating loss (18,407) (27,928)

Interest income 2,545  3,099

Net gains (losses) on equity securities 2,022  (1,425)

Interest expense (134) (17)

Other loss (439) —

Loss before income taxes (14,413) (26,271)

Income tax expense (benefit) 109  (423)

Net loss $ (14,522) $ (25,848)

Loss per share, basic and diluted $ (0.49) $ (0.90)

Weighted-average shares outstanding, basic and diluted 29,889  28,609

Stock-Based Compensation Expense

Stock-based compensation expense is included in the condensed consolidated statements of operations as follows (in thousands):

Three Months Ended

March 31,

2026 2025

(unaudited)

Cost of sales (exclusive of amortization of acquired intangible assets) $ 1,257  $ 1,456

Research and development 1,443  1,895

Selling, general and administrative 7,076  7,828

Total stock-based compensation expense $ 9,776  $ 11,179

CASTLE BIOSCIENCES, INC.

CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS

(UNAUDITED)

(in thousands)

Three Months Ended

March 31,

2026 2025

Net loss $ (14,522) $ (25,848)

Other comprehensive loss:

Net unrealized loss on marketable investment securities (330) (99)

Comprehensive loss $ (14,852) $ (25,947)

CASTLE BIOSCIENCES, INC.

CONDENSED CONSOLIDATED BALANCE SHEETS

(in thousands)

March 31, 2026 December 31, 2025

ASSETS (unaudited)

Current Assets

Cash and cash equivalents $ 63,764  $ 116,729

Marketable investment securities 197,921  182,776

Accounts receivable, net 42,264  43,382

Inventory 10,461  10,254

Prepaid expenses and other current assets 14,491  7,956

Total current assets 328,901  361,097

Long-term accounts receivable, net 1,921  1,878

Property and equipment, net 100,934  97,443

Operating lease assets 14,424  14,795

Goodwill and other intangible assets, net 97,347  99,574

Other assets – long-term 4,278  3,769

Total assets $ 547,805  $ 578,556

LIABILITIES AND STOCKHOLDERS’ EQUITY

Current Liabilities

Accounts payable $ 15,038  $ 18,711

Accrued compensation 19,111  38,287

Contingent consideration 1,000  1,000

Operating lease liabilities 1,254  1,325

Current portion of long-term debt 1,667  417

Other accrued and current liabilities 10,691  8,937

Total current liabilities 48,761  68,677

Long-term debt 8,399  9,640

Noncurrent portion of contingent consideration 1,500  1,500

Noncurrent operating lease liabilities 25,116  25,217

Noncurrent finance lease liabilities 288  314

Deferred tax liability 2,325  2,335

Total liabilities 86,389  107,683

Stockholders’ Equity

Preferred stock —  —

Common stock 30  30

Additional paid-in capital 700,255  694,860

Accumulated deficit (238,806) (224,284)

Accumulated other comprehensive (loss) income (63) 267

Total stockholders’ equity 461,416  470,873

Total liabilities and stockholders’ equity $ 547,805  $ 578,556

CASTLE BIOSCIENCES, INC.

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS

(UNAUDITED)

(in thousands)

Three Months Ended

March 31,

2026 2025

OPERATING ACTIVITIES

Net loss $ (14,522) $ (25,848)

Adjustments to reconcile net loss to net cash used in operating activities:

Depreciation and amortization 3,929  29,764

Stock-based compensation expense 9,776  11,179

Net (gains) losses on equity securities (2,022) 1,425

Deferred income taxes (10) (770)

Accretion of discounts on marketable investment securities (454) (1,435)

Other 532  30

Change in operating assets and liabilities:

Accounts receivable 1,075  (5,217)

Prepaid expenses and other current assets (6,667) (3,364)

Inventory (207) 1,286

Operating lease assets 371  420

Other assets (530) (38)

Accounts payable 3,193  615

Operating lease liabilities (172) (526)

Accrued compensation (19,176) (14,698)

Other accrued and current liabilities 2,755  1,141

Net cash used in operating activities (22,129) (6,036)

INVESTING ACTIVITIES

Purchases of marketable investment securities (55,136) (48,431)

Proceeds from maturities of marketable investment securities 39,100  36,300

Purchases of debt securities classified as held-to-maturity —  (5,569)

Proceeds from sale of equity securities 2,681  —

Purchases of property and equipment (12,455) (4,740)

Proceeds from sale of property and equipment 7  9

Net cash used in investing activities (25,803) (22,431)

FINANCING ACTIVITIES

Proceeds from exercise of common stock options 322  18

Payment of employees’ taxes on vested restricted stock units and performance-based restricted stock units (6,598) (2,515)

Proceeds from contributions to the employee stock purchase plan 1,267  970

Repayment of principal portion of finance lease liabilities (24) (26)

Net cash used in financing activities (5,033) (1,553)

NET CHANGE IN CASH AND CASH EQUIVALENTS (52,965) (30,020)

Beginning of period 116,729  119,709

End of period $ 63,764  $ 89,689

CASTLE BIOSCIENCES, INC.

Reconciliation of Non-GAAP Financial Measures (UNAUDITED)

The table below presents the reconciliation of Adjusted Revenues, Adjusted Gross Margin and Adjusted Net Loss Per Share, Basic and Diluted, which are non-GAAP financial measures. See "Use of Non-GAAP Financial Measures (UNAUDITED)" above for further information regarding the Company's use of non-GAAP financial measures.

Three Months Ended

March 31,

(in thousands, except per share data) 2026 2025

Adjusted Revenues

Net revenues (GAAP) $ 83,679 $ 87,988

Revenue associated with test reports delivered in prior periods 551 (787)

Adjusted Revenues (Non-GAAP) $ 84,230 $ 87,201

Adjusted Gross Margin

Gross margin (GAAP)1

$ 60,920 $ 43,280

Amortization of acquired intangible assets 2,226 28,325

Revenue associated with test reports delivered in prior periods 551 (787)

Adjusted Gross Margin (Non-GAAP) $ 63,697 $ 70,818

Gross Margin percentage (GAAP)2

72.8  % 49.2  %

Adjusted Gross Margin percentage (Non-GAAP)3

75.6  % 81.2  %

Adjusted Net Loss Per Share, Basic and Diluted

Net loss (GAAP) $ (14,522) $ (25,848)

Amortization of acquired intangible assets4

— 20,099

Adjusted Net Loss (Non-GAAP) $ (14,522) $ (5,749)

Weighted-average shares outstanding, basic and diluted: 29,889 28,609

Net loss per share, basic and diluted (GAAP)5

$ (0.49) $ (0.90)

Adjusted Net Loss Per Share, Basic and Diluted (Non-GAAP)6

$ (0.49) $ (0.20)

1.Calculated as net revenues (GAAP) less the sum of cost of sales (exclusive of amortization of acquired intangible assets) and amortization of acquired intangible assets.

2.Calculated as gross margin (GAAP) divided by net revenues (GAAP).

3.Calculated as Adjusted Gross Margin (Non-GAAP) divided by Adjusted Revenues (Non-GAAP).

4.Represents a one-time adjustment of an acceleration of amortization expense for our IDgenetix test during the three months ended March 31, 2025.

5.Calculated as net loss (GAAP) divided by weighted-average shares outstanding, basic and diluted.

6.Calculated as Adjusted Net Loss (Non-GAAP) divided by weighted-average shares outstanding, basic and diluted.

The table below presents the reconciliation of Adjusted EBITDA, which is a non-GAAP financial measure. See "Use of Non-GAAP Financial Measures (UNAUDITED)" above for further information regarding the Company's use of non-GAAP financial measures.

Three Months Ended

March 31,

(in thousands) 2026 2025

Adjusted EBITDA

Net loss $ (14,522) $ (25,848)

Interest income (2,545) (3,099)

Interest expense 134  17

Income tax expense (benefit) 109  (423)

Depreciation and amortization 3,929  29,764

Stock-based compensation expense 9,776  11,179

Net (gains) losses on equity securities (2,022) 1,425

Adjusted EBITDA (Non-GAAP) $ (5,141) $ 13,015

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©2026 Castle Biosciences 1 Empowering people, informing care decisions May 2026

©2026 Castle Biosciences 2 Disclaimers Forward Looking Statements This presentation contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the “safe harbor” created by those sections. These forward-looking statements include, but are not limited to, statements concerning: our anticipated 2026 revenue; our positioning for continued growth and value creation; our estimated U.S. total addressable market for our commercially available tests; our ongoing studies generating data and their impact on driving adoption of our tests; study observations and interpretations of study data, including conclusions about the benefits and impact of our tests on treatment decisions and patient outcomes; our ability to advance penetration of our tests with clinicians and payers; our ability to carry out our commercial strategies; our future approach to capital allocation; pipeline opportunities to expand screening and diagnostic support for patients; our test volume growth strategy and expectations; our ability to maintain strong adjusted gross margin and a strong balance sheet; and the timing and achievement of program milestones. The words “anticipates,” “can,” “could,” “estimates,” “expects,” “may,” “potential,” “target,” “guidance” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions, or expectations disclosed in our forward-looking statements and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. These forward-looking statements involve risks and uncertainties that could cause our actual results to differ materially from those in the forward-looking statements, including, without limitation: our estimates and assumptions underlying our estimated U.S. total addressable market for our commercially available tests; our assumptions or expectations regarding continued reimbursement for our products and subsequent coverage decisions; Novitas’ local coverage determination signifying non-coverage by Medicare of our DecisionDx-SCC test; our estimated total addressable markets for our products and product candidates; the expenses, capital requirements and potential needs for additional financing, the anticipated cost, timing and success of our product candidates; our plans to research, develop and commercialize new tests; our ability to successfully integrate new businesses, assets, products or technologies acquired through acquisitions or developed through collaborations; the effects of macroeconomic events and conditions, including inflation and monetary supply shifts, tariffs and disruptions to trade, labor shortages, liquidity concerns at, and failures of, banks and other financial institutions or other disruptions in the banking system or financing markets and recession risks, supply chain disruptions, outbreaks of contagious diseases and geopolitical events (such as the ongoing conflicts in the Middle East and Ukraine-Russia conflict), among others, on our business and our efforts to address its impact on our business; the possibility that subsequent study or trial results and findings may contradict earlier study or trial results and findings or may not support the results discussed in this presentation, including with respect to the diagnostic and prognostic tests discussed in this presentation; our planned installation of additional equipment and supporting technology infrastructures and implementation of certain process efficiencies may not enable us to increase the future scalability of our TissueCypher Test; the possibility that actual application of our tests may not provide the anticipated benefits to patients; the possibility that our newer gastroenterology and mental health franchises may not contribute to the achievement of our long-term financial targets as anticipated; and the risks set forth under the heading “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2025, and our subsequent Quarterly Reports on Form 10-Q, each filed or to be filed with the SEC, and in our other filings with the SEC. The forward-looking statements are applicable only as of the date on which they are made, and we do not assume any obligation to update any forward- looking statements, except as may be required by law.

©2026 Castle Biosciences 3 Disclaimers Financial Information; Non-GAAP Financial Measures In this presentation, we use the metrics of Adjusted Revenues, Adjusted Gross Margin and Adjusted EBITDA, which are non-GAAP financial measures and are not calculated in accordance with generally accepted accounting principles in the United States (GAAP). Adjusted Revenues and Adjusted Gross Margin reflect adjustments to GAAP net revenues to exclude net positive and/or net negative revenue adjustments recorded in the current period associated with changes in estimated variable consideration related to test reports delivered in previous periods. Adjusted Gross Margin further excludes acquisition-related intangible asset amortization. Adjusted EBITDA excludes from net loss: interest income, interest expense, income tax expense (benefit), depreciation and amortization expense, stock-based compensation expense and net (gains) losses on equity securities. We use Adjusted Revenues, Adjusted Gross Margin and Adjusted EBITDA internally because we believe these metrics provide useful supplemental information in assessing our revenue and operating performance reported in accordance with GAAP, respectively. We believe that Adjusted Revenues, when used in conjunction with our test report volume information, facilitates investors’ analysis of our current-period revenue performance and average selling price performance by excluding the effects of revenue adjustments related to test reports delivered in prior periods, since these adjustments may not be indicative of the current or future performance of our business. We believe that providing Adjusted Revenues may also help facilitate comparisons to our historical periods. Adjusted Gross Margin is calculated using Adjusted Revenues and therefore excludes the impact of revenue adjustments related to test reports delivered in prior periods, which we believe is useful to investors as described above. We further exclude acquisition-related intangible asset amortization in the calculation of Adjusted Gross Margin. We believe that excluding acquisition-related intangible asset amortization may facilitate gross margin comparisons to historical periods and may be useful in assessing current-period performance without regard to the historical accounting valuations of intangible assets, which are applicable only to tests we acquired rather than internally developed. We believe Adjusted EBITDA may enhance an evaluation of our operating performance because it excludes the impact of prior decisions made about capital investment, financing, investing and certain expenses we believe are not indicative of our ongoing performance. However, these non-GAAP financial measures may be different from non-GAAP financial measures used by other companies, even when the same or similarly titled terms are used to identify such measures, limiting their usefulness for comparative purposes. These non-GAAP financial measures are not meant to be considered in isolation or used as substitutes for net revenues, gross margin, or net income (loss) reported in accordance with GAAP; should be considered in conjunction with our financial information presented in accordance with GAAP; have no standardized meaning prescribed by GAAP; are unaudited; and are not prepared under any comprehensive set of accounting rules or principles. In addition, from time to time in the future, there may be other items that we may exclude for purposes of these non- GAAP financial measures, and we may in the future cease to exclude items that we have historically excluded for purposes of these non-GAAP financial measures. Likewise, we may determine to modify the nature of adjustments to arrive at these non-GAAP financial measures. Because of the non-standardized definitions of non-GAAP financial measures, the non-GAAP financial measure as used by us in this press release and the accompanying reconciliation tables have limits in their usefulness to investors and may be calculated differently from, and therefore may not be directly comparable to, similarly titled measures used by other companies. Accordingly, investors should not place undue reliance on non-GAAP financial measures. Reconciliations of these non-GAAP financial measures to the most directly comparable GAAP financial measures are presented in the tables at the end of this presentation. Industry and Market Data This presentation includes certain information and statistics obtained from third-party sources. The Company has not independently verified the accuracy or completeness of any such third- party information.

©2026 Castle Biosciences 4 Registered Trademarks DecisionDx-Melanoma, DecisionDx-CMSeq, i31-SLNB, i31-ROR, DecisionDx-SCC, MyPath Melanoma, AdvanceAD-Tx, TissueCypher, Esopredict, DecisionDx-UM, DecisionDx-PRAME and DecisionDx-UMSeq are trademarks of Castle Biosciences, Inc.

©2026 Castle Biosciences 5 Improving health through innovative tests that guide patient care OUR MISSION Transforming disease management by keeping people first: patients, clinicians, employees, and investors OUR VISION

©2026 Castle Biosciences 6 First Quarter 2026 Results Highlights Castle Biosciences received a 2026 USA TODAY Top Workplaces USA Award for the fifth consecutive year 5 Published new data from a prospective, multicenter study confirming DecisionDx-Melanoma’s i31-SLNB accurately predicts SLN positivity and identifies low-risk patients who may safely consider forgoing SLNB. Patients with a less than 5% predicted risk had an actual SLN positivity rate of just 2.6%, supporting alignment with NCCN Guideline thresholds. 6 As of March 31, 2026, cash, cash equivalents and marketable investment securities totaled $261.7 million 2 3 4 1 Total test reports for our core revenue drivers (DecisionDx-Melanoma, TissueCypher) increased 36% in 1Q26 year over year Raised 2026 total revenue guidance to $345-355 million, up from $340- 350 million previously reported Both DecisionDx-Melanoma and TissueCypher achieved double digit year-over-year test volume growth, 16% and 58%, respectively, with March being a record month for both tests

©2026 Castle Biosciences 7 Proven strategy designed to drive value creation for our stakeholders FOCUS on best/first-in-class tests with high, unmet clinical need and significant market opportunity BUILD robust clinical evidence PENETRATE target markets to further test adoption by clinicians and payers

©2026 Castle Biosciences 8 Answering clinical questions to guide care along the patient journey 1. Collaboration and license agreement with SciBase Holding AB (“SciBase”) announced in June 2025 RESCUE/ PREVENTION DIFFERENTIAL DIAGNOSTIC SUPPORT RISK STRATIFICATION THERAPY SELECTION GUIDANCE MRD=minimal residual disease SCREENING SUPPORT Dermatology Ophthalmology Pipeline test to diagnose GI disease (non-endoscopic cell collection device) Pipeline test to diagnose GI disease (non-endoscopic cell collection device) SciBase Collaboration Atopic Dermatitis (AD) Flares Pipeline1 Gastroenterology

©2026 Castle Biosciences 9 Clinical portfolio and pipeline tests Franchise Test Indication/Utility ~U.S. TAM1/Use Population Discovery Development Commercial Dermatology Cutaneous melanoma/ risk of sentinel lymph node positivity, recurrence & metastasis ~$540M/ 130k patients w/ invasive CM Cutaneous squamous cell carcinoma/ risk of metastasis & local recurrence; likelihood of benefit from ART ~$820M/ 200k patients with high-risk SCC Ambiguous melanocytic lesions/ malignant potential ~$600M/ 300k patients w/ ambiguous lesions Atopic dermatitis/ therapy guidance ~$33B/ ~10 million patients ages 12+ in U.S. one- year prevalence SciBase collaboration pipeline test Atopic dermatitis/ prediction of flares Gastroenterology Barrett’s esophagus/ risk of progression to high-grade dysplasia or esophageal adenocarcinoma ~$1B Pipeline test (non-endoscopic collection device) GI disease/ diagnostic test Ophthalmology Uveal melanoma/ risk of metastasis ~$10M 1. U.S. TAM= Total addressable market based on estimated patient population assuming average reimbursement rate among all payors.

©2026 Castle Biosciences 10 DecisionDx-Melanoma DERMATOLOGY Provides comprehensive, personalized, genomic tumor information to guide management for patients with cutaneous melanoma demonstrated change in management for 1 of 2 patients tested3 ~242,000 patients with a clinical DecisionDx- Melanoma order from ~17,150 clinicians4 50% Clinical Validity, Utility and Demonstrated Patient Outcomes Demonstrated clinical validity, utility and impact, backed by 58 peer-reviewed publications1, including two publications (Bailey et al. 2023 and Dhillon et al. 2023) demonstrating an association with testing and improved patient outcomes SLNB Guidance and Patient Outcomes2 New data from Castle’s ongoing prospective multicenter study evaluating DecisionDx-Melanoma’s i31- SLNB test result show the test accurately predicts SLN positivity, outperforms staging criteria and other GEP tests, and identifies patients below the 5% NCCN threshold who may safely forgo SLNB with favorable long-term outcomes 1. As of December 31, 2025, 2. Beard T, Guenther JM, Leong SP, et al. The integrated 31-gene expression profile test identifies low-risk patients with cutaneous melanoma who can forego the SLNB procedure: results from a prospective, multicenter trial. Future Oncol. Published online [March 13, 2026]. doi: https://doi.org/10.1080/14796694.2026.2640227.; 3. Dillon et al. 2022; 4. Data as of March 31, 2026; 5. U.S. TAM = Total addressable market based on estimated patient population assuming average reimbursement rate among all payors. SLN(B)=sentinel lymph node (biopsy) ~$540M Estimated U.S. TAM5

©2026 Castle Biosciences 11 Individual risk of SLNB positivity Individual risk of recurrence ? 31-GEP Class Score Ulceration Breslow thickness Age Mitotic rate Ulceration Age Breslow thickness Mitotic rate SLN status Tumor location Collaborative study with the National Cancer Institute’s SEER Program Registries is the largest real- world study of GEP testing in melanoma (n=4,687): • SEER cohort of unselected, prospectively tested patients shows improved survival for patients tested with DecisionDx-Melanoma compared to untested patients​ with 29% lower 3-year melanoma-specific and 17% lower 3-year overall mortality, and • DecisionDx-Melanoma provided significant, independent risk stratification of patients with cutaneous melanoma SLN- patients with a high-risk DecisionDx-Melanoma result had routine imaging surveillance added to their treatment plan. These patients: • Had their recurrence detected ~10 months earlier, with 62% lower tumor burden • Were more likely to start immunotherapy when offered (76.3% vs 67.9%) • Saw improved overall survival outcomes at 45 months (86.8% vs 75%) Whitman et al. JCO Precis. Oncol. 2021; Jarell et al. J. Am. Acad. Dermatol. 2022 Bailey et al. JCO Precis. Oncol. 2023; Dhillon et al. Arch Dermatol Res. 2023 “Patients who received routine imaging after high- risk GEP test scores had an earlier recurrence diagnosis with lower tumor burden, leading to better clinical outcomes.” Clinical use of DecisionDx-Melanoma is associated with improved patient survival DecisionDx-Melanoma provides precise, personalized risk prediction for two critical clinical questions

12©2026 Castle Biosciences DECIDE study showed up to 13-fold difference in predicting SLNB positivity rates between lowest and highest categories DECIDE study showed up to 13-fold difference in predicting SLNB positivity rates between lowest and highest categories Beard et al. Future Oncology 2026, Beard et al. SSO Annual Conference 2026. Phoenix, AZ. SLN positivity rates by i31-SLNB result <5% 5-10% >10% Fold Difference <5% vs. >10% T1-T4 2.6% 7.0% 21.4% 8x higher% SLN+ T1b-T2a 1.4% 7.4% 18.5% 13x higher % SLN+ Patients with >10% predicted risk had 8-13x higher SLN positivity Patients with <5% predicted risk had very low SLN positivity

13©2026 Castle Biosciences Prospective data confirm that DecisionDx-Melanoma i31-SLNB result improves SLNB decision-making and supports favorable patient outcomes Prospective data confirm that DecisionDx- Melanoma i31-SLNB result improves SLNB decision- making and supports favorable patient outcomes Beard et al. Future Oncology 2026 1 Accurate risk stratification Patients with a <5% i31-SLNB result have high recurrence-free survival (97.8%) at 3 years 3 Favorable patient outcomes Low-risk test results are associated with very low SLNB positive outcomes. The i31-SLNB gives physicians greater confidence in identifying which patients can avoid SLNB. 2 Confidence in clinical decision-making

©2026 Castle Biosciences 14 TissueCypher GASTROENTEROLOGY A leading risk-stratification test designed to predict risk of progression to esophageal cancer in patients with Barrett’s esophagus Clinical Validity and Utility Demonstrated validity, utility and impact, backed by 17 peer-reviewed publications1 demonstrating the ability and performance of the test in risk-stratifying patients with Barrett’s esophagus to guide risk-appropriate treatment decisions Recognition from AGA 2024 Clinical Practice Guideline acknowledges that individuals who may be at increased risk of progression to esophageal cancer might be identified using tissue- based biomarkers, particularly TissueCypher 2022 Recognized in the Clinical Practice Update on New Technology and Innovation for Surveillance and Screening in Barrett’s Esophagus as a tool that may be used by physicians to risk stratify non-dysplastic patients ~415,000 patients receiving upper GI endoscopies per year who meet intended use criteria for TissueCypher 1 in 40 patients progress to esophageal cancer within 5 years (among BE patients)2 ~$1B 1. As of December 31, 2025, 2. Shaheen et al. Gastroenterology 2000; 3. U.S. TAM = Total addressable market based on estimated patient population assuming average reimbursement rate among all payors; 4. Data as of March 31, 2026. Estimated U.S. TAM3 Ordering clinicians4 ~4,900

©2026 Castle Biosciences 15 TissueCypher provides individualized 5-year risk of progression to HGD or EAC Low RiskHigh Risk • High Risk score enables increased surveillance or early intervention to prevent cancer1 • Low Risk score minimizes over-treatment and supports extension of surveillance intervals to guideline recommendations1 Indicated for NDBE, IND, and LGD 1. Rubenstein JH, et al. Gastroenterology. 2024.

©2026 Castle Biosciences 16 TissueCypher provides independent prediction of progression n=699 patients1-6, 150 incident progressors, 40 prevalent cases, 509 non-progressors No significant risk stratification 62% progressors detected 7.8x ↑ risk 2.7x ↑ risk 1. Critchley-Thorne RJ, et al. Cancer Epidemiol Biomarkers Prev. 2016; 2. Critchley-Thorne RJ, et al. Cancer Epidemiol Biomarkers Prev. 2017; 3. Davison JM, et al. Am J Gastroenterol. 2020; 4. Frei NF, et al. Clin Transl Gastroenterol. 2020; 5. Frei NF, et al. Am J Gastroenterol. 2021; 6. Davison JM, et al. Clin & Transl Gastroenterol. 2023. Real world histologic grading TissueCypher risk class

©2026 Castle Biosciences 17 AdvanceAD-Tx DERMATOLOGY A non-invasive molecular test that is designed to detect the underlying immune biology of atopic dermatitis (AD) that is driving an individual patient’s AD and thus helps to guide systemic treatment decision making in patients with moderate- to-severe AD Validated in Real-World Patients • The AdvanceAD-Tx test has been clinically validated in patients 12 years and older with moderate-to-severe AD. The clinical validation study included both systemic treatment naïve patients and those who were on a systemic treatment but considering a switch in therapy. • The test can be ordered at any point in the patient’s treatment journey and provides valuable molecular insight to help guide therapy-class selection. Ordering the test early may help reduce uncertainty, minimize trial-and-error, and support more timely disease control. ~10m patient population of moderate-to- severe AD patients 12+ year of age, based on one-year prevalance1 ~$33 billion 1. Atopic Dermatitis in America Study: A Cross-Sectional Study Examining the Prevalence and Disease Burden of Atopic Dermatitis in the US Adult Population. DOI:https://doi.org/10.1016/j.jid.2018.08.028. Patient burden and quality of life in atopic dermatitis in US adults: A population-based cross-sectional study. DOI:https://doi.org/10.1016/j.jid.2018.08.028; https://www.census.gov/data/tables/time- series/demo/popest/2020s-national-detail.html 2. https://pmc.ncbi.nlm.nih.gov/articles/PMC11904833/pdf/ActaDV-105-41504.pdf; 3. U.S. TAM = Total addressable market based on estimated patient population assuming average reimbursement rate among all payors. of patients who started on an advanced biologic or JAKi switched to another advanced systemic therapy2 ~27% Estimated U.S. TAM3

18©2026 Castle Biosciences AdvanceAD-Tx results are intended to aid, not replace, clinical judgment. All treatment decisions should be made by the clinician in the context of the patient’s overall clinical picture. AdvanceAD-Tx guides systemic treatment choice for patients with moderate-to-severe atopic dermatitis AdvanceAD-Tx guides systemic treatment choice for patients with moderate-to-severe atopic dermatitis Moderate-to- severe AD patient ≥12 years JAK Inhibitor Responder Profile Gene expression profile is associated with a significantly higher clinical benefit from JAK inhibitor treatment Th2 Molecular Profile Gene expression profile is associated with similar clinical benefit regardless of treatment with a Th2-targeted or JAK inhibitor therapy • Quantifies expression of 487 genes from 12 immune, inflammatory, and cutaneous pathways associated with AD • Applies a validated neural network algorithm • Guides systemic treatment decision making

19©2026 Castle Biosciences AdvanceAD-Tx identifies patients who have a superior response to JAK inhibitor therapies AdvanceAD-Tx identifies patients who have a superior response to JAK inhibitor therapies Silverberg JI, Eichenfield LF, Armstrong AW, et al. The 487-gene expression profile test guides systemic therapy selection to improve outcomes for patients with atopic dermatitis: results from a prospective trial. J Am Acad Dermatol. 2026. doi:10.1016/j.jaad.2026.02.034. Presented at Fall Clinical Dermatology Conference 2025. Data on file. 5.5x Improvement in skin clearance (EASI-90) More patients achieved ≥90% improvement in skin clearance 1 in 2 Reported “no itch” compared to 0 More patients reported “no itch” in the last week 3.8x Faster time to EASI-90 Patients reached clearance more quickly 5.5x Improvement in quality of life (DLQI 0) More patients reported no impact on daily life CONTINUE 1 in 3 Experienced clear skin compared to 0 More patients achieved completely clear skin (vIGA- AD 0) Clinician Reported Outcomes Patient Reported Outcomes Patients with JAK Inhibitor Responder Profile who are treated with a JAK inhibitor therapy, compared to those treated with a Th2-targeted therapy achieve the following by 3 months: 3.3x Improvement in flare-free rate More patients remained flare-free

©2026 Castle Biosciences 20 Financials

©2026 Castle Biosciences 21 First Quarter 2026 Financial Highlights Total Revenue Cash Position5 Operating Cash Flow4 Total Report Volume Adjusted Gross Margin1,2 Adjusted EBITDA3 $83.7M $261.7M$(22.1)M26,933 75.6% $(5.1)M 1. Adjusted Gross Margin is a non-GAAP measure. See Non-GAAP reconciliations at the end of this presentation for a reconciliation of Adjusted Gross Margin to its most closely comparable GAAP measure. 2. Calculated as Adjusted Gross Margin (Non-GAAP) divided by Adjusted Revenues (Non-GAAP) 3. Adjusted EBITDA is a non-GAAP measure. See non-GAAP reconciliations at the end of this presentation for a reconciliation of Adjusted EBITDA to its most closely comparable GAAP measure. 4. Net cash used in operating activities in 1Q26 includes payout of annual bonuses as well as certain healthcare benefit contributions that that are not expected to recur during the remainder of 2026. 5. As of March 31, 2026; includes Cash, Cash Equivalents & Marketable Investment Securities Track record of consistent execution and strong business fundamentals 1Q26

©2026 Castle Biosciences 22 First Quarter 2026 Test Volume Results 1Q26 1Q25 Core Revenue Drivers: • DecisionDx-Melanoma 10,021 8,621 • TissueCypher 11,745 7,432 Additional Tests: • DecisionDx-SCC1 3,702 4,375 • MyPath Melanoma 973 926 • DecisionDx-UM 492 470 1. Affecting first quarter ended March 31, 2026 test report volume was the change in Medicare coverage effective April 24, 2025, and re-focus of our commercial efforts.

©2026 Castle Biosciences 23 A disciplined approach to capital allocation Commercial optimization Focused R&D efforts to build evidentiary support and develop tests Strategic opportunities, including within our current therapeutic areas

©2026 Castle Biosciences 24 Well positioned for continued value creation Drive robust test volume growth Maintain strong Adjusted Gross Margin Maintain strong balance sheet Follow disciplined capital allocation

©2026 Castle Biosciences 25 Appendix

©2026 Castle Biosciences 26 DecisionDx-SCC DERMATOLOGY Identifies the risk of metastasis in patients with squamous cell carcinoma (SCC) and one or more risk factors Clinical Validity and Utility Demonstrated validity, utility and impact, backed by 24 peer-reviewed publications1, including data showing that DecisionDx-SCC can significantly impact patient management plans in a risk-appropriate manner within established guidelines Real-World Use Framework Several published studies in 2024 supported the use of DecisionDx-SCC to predict likelihood of benefit from adjuvant radiation therapy (ART); two of these studies represent the largest2 and second largest3 studies completed to date to evaluate the effectiveness of ART in SCC Estimated U.S. TAM5 ~200,000 ~54% ~$820M patients diagnosed annually with SCC and classified as high risk in the U.S. of clinicians ordering DecisionDx-SCC also ordered DecisionDx- Melanoma4 1. As of December 31, 2025, 2. Arron et al. International Journal of Radiation Oncology, Biology & Physics 2024; 3. Ruiz et al. Future Oncology 2024; 4. three-months ended March 31, 2026; 5. U.S. TAM = Total addressable market based on estimated patient population assuming average reimbursement rate among all payors; 6. Data as of March 31, 2026. patients with a clinical DecisionDx- SCC order from ~7,600 clinicia s6 ~63,000

©2026 Castle Biosciences 27 DecisionDx-SCC addresses three critical clinical questions for high-risk SCC patients DecisionDx-SCC Class results predict an SCC patient’s individual risk of metastasis, local recurrence and individual benefit from adjuvant radiation therapy (ART) *Treated with Mohs surgery with no residual disease (R0) Overall Event Rate: 13.2%, n=897 1 What is my SCC patient’s risk of regional or distant metastasis? Low 6.5% Higher 19.4% Highest 45.9% Overall Event Rate: 8.9%, n=414 2 What is my NCCN high risk SCC patient’s risk of local recurrence*? Low 5.8% Higher 14.5% Highest 28.6% 3 Is my SCC patient likely to benefit from adjuvant radiation therapy (ART)? No discernible benefit Potential benefit Likely to benefit

©2026 Castle Biosciences 28 DecisionDx-SCC may identify patients who benefit most from ART to control metastatic disease progression • A Class 2B result reflects a significant decrease in median risk of metastatic disease progression between resampled cohorts that did and did not receive ART M E D IA N M E T P R O G R E S S R A T E ( % ) TIME (YEARS) 1.00 0.75 0.50 0.25 0.0 0 0 1 2 3 4 5 MEDIAN RISK OF METASTATIC DISEASE PROGRESSION ART: Class 1 noART: Class 1 noART: Class 2A ART: Class 2A ART: Class 2B noART: Class 2B • A Class 1 or Class 2A result did not reflect a significant decrease in median risk of metastatic disease progression between resampled cohorts that did and did not receive ART 100 5 5

©2026 Castle Biosciences 29 MyPath Melanoma DERMATOLOGY Aids in the diagnosis and management for patients with ambiguous melanocytic lesions Clinical Validity and Utility Demonstrated validity, utility and impact, backed by 20 peer-reviewed publications1 demonstrating the performance and utility of the test in providing objective information to aid in diagnosis in ambiguous melanocytic lesions Guideline Support • National Comprehensive Cancer Network guidelines for cutaneous melanoma in the principles for molecular testing • American Society of Dermatopathology in the Appropriate Use Criteria for ancillary diagnostic testing • American Academy of Dermatology guidelines of care for the management of primary cutaneous melanoma Estimated U.S. TAM3 ~300,000 patients each year present with a diagnostically ambiguous lesion 50,000+ lesions tested clinically2 ~$600M 1. As of December 31, 2025, 2. As of March 31, 2026; 3. U.S. TAM = Total addressable market based on estimated patient population assuming average reimbursement rate among all payors.

©2026 Castle Biosciences 30 DecisionDx-UM OPHTHALMOLOGY The standard of care for evaluating metastatic risk in uveal melanoma Standard of Care • Utilized in approximately 80% of newly diagnosed patients • Included in NCCN Guidelines and considered standard of care peer-reviewed publications ~8 in 10 ~2,000 39 patients diagnosed in the U.S. annually patients diagnosed with UM in the U.S. receive the test as part of their diagnostic workup Clinical Validity and Utility Demonstrated validity, utility and impact, backed by 39 peer-reviewed publications, which included more than 5,500 patients, representing the largest body of evidence for a molecular prognostic test in this field All data as of March 31, 2026, except peer-reviewed publications, which is as of December 31, 2025

©2026 Castle Biosciences 31 Reconciliation of Non-GAAP Financial Measures (Unaudited) The table below presents the reconciliation of Adjusted Revenues and Adjusted Gross Margin, which are non-GAAP financial measures. See “Financial information; Non-GAAP Financial Measures" above for further information regarding the Company's use of non-GAAP financial measures. (In thousands) Three months ended Mar. 31, 2026 Dec. 31, 2025 Sep. 30, 2025 Jun. 30, 2025 Mar. 31, 2025 Adjusted Revenues Net revenues (GAAP) $83,679 $87,010 $83,043 $86,188 $87,988 Revenue associated with test reports delivered in prior periods 551 (5,134) (2,498) (6) (787) Adjusted Revenues (Non-GAAP) $84,230 $81,876 $80,545 $86,182 $87,201 Adjusted Gross Margin Gross margin (GAAP)1 $60,920 $66,419 $62,063 $66,601 $43,280 Amortization of acquired intangible assets 2,226 2,276 2,276 1,961 28,325 Revenue associated with test reports delivered in prior periods 551 (5,134) (2,498) (6) (787) Adjusted Gross Margin (Non-GAAP) $63,697 $63,561 $61,841 $68,556 $70,818 Gross Margin percentage (GAAP)2 72.8% 76.3% 74.7% 77.3% 49.2% Adjusted Gross Margin percentage (Non-GAAP)3 75.6% 77.6% 76.8% 79.5% 81.2%

©2026 Castle Biosciences 32 Reconciliation of Non-GAAP Financial Measures (Unaudited) The table below presents the reconciliation of Adjusted EBITDA, which is a non-GAAP financial measure. See “Financial information; Non-GAAP Financial Measures" above for further information regarding the Company's use of non-GAAP financial measures. (In thousands) Three months ended Mar. 31, 2026 Dec. 31, 2025 Sep. 30, 2025 Jun. 30, 2025 Mar. 31, 2025 Adjusted EBITDA Net (loss) income $(14,522) $(2,332) $(501) $4,523 $(25,848) Interest income (2,545) (2,896) (2,833) (2,944) (3,099) Interest expense 134 24 24 21 17 Income tax expense (benefit) 109 (382) 115 (4,666) (423) Depreciation and amortization 3,929 3,777 3,816 3,414 29,764 Stock-based compensation expense 9,776 11,406 12,100 11,208 11,179 Net (gains) losses on equity securities (2,022) 1,855 (3,561) (1,185) 1,425 Adjusted EBITDA (Non-GAAP) $(5,141) $11,452 $9,160 $10,371 $13,015

©2026 Castle Biosciences 33 Thank You

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