Slide 1: Empowering people, informing care decisions
Empowering people, informing care decisions February 2026 ©2026 Castle Biosciences 1
Slide 2: Disclaimers: Forward Looking Statements
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 sectio
Slide 3: Disclaimers: Non-GAAP Financial Measures
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 Uni
Slide 4: Registered Trademarks
Registered Trademarks DecisionDx-Melanoma, DecisionDx-CMSeq, i31-SLNB, i31-ROR, DecisionDx-SCC, MyPath Melanoma, AdvanceAD-Tx, TissueCypher, DecisionDx-UM, DecisionDx-PRAME and DecisionDx-UMSeq are trademarks of Castle Biosciences, Inc. ©2026 Castle Biosciences 4
Slide 5: Improving health through innovative tests that guide patient care
OUR MISSION Improving health through innovative tests that guide patient care OUR VISION Transforming disease management by keeping people first: patients, clinicians, employees, and investors ©2026 Castle Biosciences 5
Slide 6: Fourth Quarter and Full-Year 2025 Results Highlights
Fourth Quarter and Full–Year 2025 Results Highlights 1 Total test reports for our core revenue drivers (DecisionDx-Melanoma, 1 TissueCypher) increased 42% in Q4 2025 year over year, driving 37% growth for full year 2025 Achieved provided guidance of high single-digit percentage volume 2 growth at 9%
Slide 7: Proven strategy designed to drive value creation for our stakeholders
Proven strategy designed to drive value creation for our stakeholders BUILD robust clinical FOCUS evidence on best/first-in-class tests with high, unmet clinical need and significant market opportunity PENETRATE target markets to further test adoption by clinicians and payers ©2026 Castle Bioscience
Slide 8: Answering clinical questions to guide care along the patient journey
Answering clinical questions to guide care along the patient journey DIFFERENTIAL RISK THERAPY RESCUE/ SCREENING DIAGNOSTIC SELECTION SUPPORT STRATIFICATION GUIDANCE PREVENTION SUPPORT Dermatology SciBase Collaboration Atopic Dermatitis (AD) Flares Pipeline1 Pipeline test to diagnose Pipeline test t
Slide 9: Clinical portfolio and pipeline tests
Clinical portfolio and pipeline tests ~U.S. TAM1/Use Franchise Test Indication/Utility Discovery Development Commercial Population Cutaneous melanoma/ ~$540M/ risk of sentinel lymph node positivity, 130k patients w/ recurrence & metastasis invasive CM Cutaneous squamous cell carcinoma/ ~$820M/ risk
Slide 10: DecisionDx-Melanoma
DERMATOLOGY DecisionDx-Melanoma Provides comprehensive, personalized, genomic tumor information to guide management for patients with cutaneous melanoma Clinical Validity, Utility and SLNB Guidance and Demonstrated Patient Patient Outcomes1,2 Outcomes DecisionDx-Melanoma Demonstrated clinical validi
Slide 11: DecisionDx-Melanoma provides precise, personalized risk prediction for two critical clinical questions
DecisionDx-Melanoma provides precise, personalized risk prediction for two critical clinical questions Collaborative study with the National Cancer Institute’s SEER Program Registries is the largest real- Clinical use of DecisionDx-Melanoma is associated with improved patient survival world study of
Slide 12: Evidence from prospective studies supporting DecisionDx-Melanoma demonstrates
Evidence from prospective studies supporting DecisionDx-Melanoma demonstrates: 1 2 3 Physicians are using DecisionDx- DecisionDx- DecisionDx-Melanoma Melanoma low-risk Melanoma low-risk, to inform clinical test results are Class 1A patients decisions about associated with who forego a SLNB sentinel
Slide 13: TissueCypher
GASTROENTEROLOGY TissueCypher A leading risk-stratification test designed to predict risk of progression to esophageal cancer in patients with Barrett’s esophagus Clinical Validity and Utility Recognition from AGA Demonstrated validity, 2024 Clinical Practice Guideline utility and impact, backed ack
Slide 14: TissueCypher provides individualized 5-year risk of progression to HGD or EAC
TissueCypher provides individualized 5-year risk of progression to HGD or EAC Indicated for NDBE, IND, and LGD • 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 guide
Slide 15: TissueCypher provides independent prediction of progression
TissueCypher provides independent prediction of progression Real world histologic grading TissueCypher risk class 7.8x ↑ risk 2.7x ↑ risk No significant risk stratification 62% progressors detected n=699 patients1-6, 150 incident progressors, 40 prevalent cases, 509 non-progressors 1. Critchley-Thor
Slide 16: AdvanceAD-Tx
DERMATOLOGY AdvanceAD-Tx 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-Wo
Slide 17: AdvanceAD-Tx guides systemic treatment choice for moderate-to-severe atopic dermatitis
AdvanceAD-Tx guides systemic treatment choice for patients with moderate-to-severe atopic dermatitis JAK Inhibitor Responder Profile Gene expression profile is associated Moderate-to- with a significantly higher clinical severe AD patient benefit from JAK inhibitor treatment ≥12 years • Quantifies e
Slide 18: Data from the IDENTITY Study
Data from the IDENTITY Study Patients with JAKi 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: More likely to achieve a validated More likely to More likely to Achieved a investigator remain fla
Slide 19: Financials
Financials ©2026 Castle Biosciences 19
Slide 20: Fourth Quarter and Year-end 2025 Financial Highlights
Fourth Quarter and Year-end 2025 Financial Highlights Track record of consistent execution and strong business fundamentals Adjusted Total Total Report Adjusted Operating Cash Gross Revenue Volume EBITDA3 Cash Flow Position4 Margin1,2 4Q25 $87.0M 27,236 77.6% $11.5M $26.9M $299.5M 2025 $344.2M 105,0
Slide 21: Fourth Quarter and Year-end 2025 Test Volume Results
Fourth Quarter and Year-end 2025 Test Volume Results 4Q25 4Q24 2025 2024 Total Test Reports 27,236 24,071 105,053 96,071 DecisionDx-Melanoma 10,022 8,672 39,083 36,008 TissueCypher 11,803 6,672 39,014 20,956 DecisionDx-SCC1 3,971 4,299 17,294 16,348 MyPath Melanoma 1,045 879 4,288 3,909 DecisionDx-U
Slide 22: A disciplined approach to capital allocation
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 22
Slide 23: Well positioned for continued value creation
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 23
Slide 24: Appendix
Appendix ©2026 Castle Biosciences 24 24
Slide 25: DecisionDx-SCC
DERMATOLOGY DecisionDx-SCC Identifies the risk of metastasis in patients with squamous cell carcinoma (SCC) and one or more risk factors Clinical Validity and Utility Real-World Use Framework Demonstrated validity, Several published studies in utility and impact, backed by 24 peer-reviewed 2024 supp
Slide 26: DecisionDx-SCC addresses three critical clinical questions for high-risk SCC patients
DecisionDx-SCC addresses three critical clinical questions for high-risk SCC patients 1 2 3 What is my SCC patient’s What is my NCCN high risk risk of regional or distant SCC patient’s risk of local Is my SCC patient likely to metastasis? recurrence*? benefit from adjuvant radiation therapy (ART)? O
Slide 27: DecisionDx-SCC may identify patients who benefit most from ART
DecisionDx-SCC may identify patients who benefit most from ART to control metastatic disease progression noART: Class 2B ART: Class 2B MEDIAN RISK OF METASTATIC DISEASE PROGRESSION 100 ART: Class 2A • A Class 1 or Class 2A result did not 1.00 noART: Class 2A reflect a significant decrease in MEDIAN
Slide 28: MyPath Melanoma
DERMATOLOGY MyPath Melanoma Aids in the diagnosis and management for patients with ambiguous melanocytic lesions Clinical Validity and Utility Guideline Support Demonstrated validity, • National Comprehensive utility and impact, backed Cancer Network guidelines by 20 peer-reviewed for cutaneous mela
Slide 29: DecisionDx-UM
OPHTHALMOLOGY DecisionDx-UM The standard of care for evaluating metastatic risk in uveal melanoma Clinical Validity and Utility Demonstrated validity, utility and impact, backed Standard of Care by 39 peer-reviewed publications, which • Utilized in approximately 80% of newly diagnosed ~8 in 10 ~2,00
Slide 30: Reconciliation of Non-GAAP Financial Measures (Unaudited)
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 "Use of Non- GAAP Financial Measures (UNAUDITED)" above for further information regarding the Company's use
Slide 31: Reconciliation of Non-GAAP Financial Measures (Unaudited)
Reconciliation of Non-GAAP Financial Measures (Unaudited) 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 measur
Slide 32: Thank You
Thank You ©2026 Castle Biosciences 32