Business Description

As used in this Annual Report on Form 10-K, unless the context indicates or otherwise requires, “Castle Biosciences,” the “Company,” “we,” “us” and “our” refer to Castle Biosciences, Inc., a Delaware Corporation. Overview Castle Biosciences is a molecular diagnostics company offering innovative test solutions to aid clinicians in the diagnosis and treatment of dermatologic cancers, Barrett’s esophagus (“BE”), atopic dermatitis (“AD”), uveal melanoma (“UM”). Since our inception in 2008, it has been our vision to transform disease management by keeping people first: patients, clinicians, employees and investors. This foundational strategy remains the guidepost for the direction of our company and the basis of long-term value creation. Our Testing Solutions Our tests are designed to deliver personalized information to help better inform clinical care decisions. For our core tissue-based tests, we use multi-analyte assays with algorithmic analysis (“MAAA”) to characterize an individual patient’s biology and generate clinically actionable information. Depending on the specific test, this information may be used to provide information to help guide treatment and patient management decisions including potential responsiveness to therapy and to assist in the diagnosis of a disease. Test Portfolio and Market Overview Our portfolio consists of test offerings to aid clinicians in the diagnosis and treatment of cancers or precancerous diagnoses in the fields of dermatology, gastroenterology and ophthalmology, and most recently includes a test to guide systemic treatment decisions in patients with moderate-to-severe AD. Maintaining commercial success for our existing test portfolio requires generating ongoing evidence, such as clinical performance and clinical use documentation, to support appropriate clinician adoption, reimbursement success and guideline inclusion. The clinical validity and utility of our test portfolio is supported by peer-reviewed publications and ongoing clinical studies. Collectively, approximately 158 peer-reviewed articles have been published demonstrating the analytical validity, clinical validity and clinical utility of the tests in our portfolio. The following table summarizes our commercially available tests: Dermatology Gastroenterology Ophthalmology DecisionDx-Melanoma TissueCypher DecisionDx-UM AdvanceAD-Tx (1) DecisionDx-SCC MyPath Melanoma (1) We commenced a limited launch of our AdvanceAD-Tx TM test in November 2025. DecisionDx-Melanoma DecisionDx-Melanoma is our proprietary risk stratification gene expression profile (“GEP”) test designed to predict the likelihood of a positive sentinel lymph node and the risk of metastasis or recurrence for patients diagnosed with invasive cutaneous melanoma (“CM”), a deadly skin cancer. In a typical year, we estimate approximately 130,000 patients are diagnosed with invasive CM in the U.S., representing an estimated U.S. TAM of approximately $540 million. This estimated annual incidence number is based upon a calculation using data from the U.S. Surveillance, Epidemiology, and End Results registries and subsequently adjusted for the documented underreporting of melanoma diagnoses, which ranges from 30%-72%. Based on the substantial clinical evidence that we have developed, we have received Medicare coverage for DecisionDx-Melanoma. We estimate that approximately 50% of patients diagnosed with CM are 65 years of age or older. As of December 31, 2025, 58 peer-reviewed articles, five of which were published in 2025, support the clinical validity, clinical utility and impact on outcomes of our DecisionDx-Melanoma test. 5 Table of Contents TissueCypher TissueCypher is our proprietary risk stratification spatialomics test designed to predict future development of high-grade dysplasia (“HGD”) and/or esophageal cancer in patients with non-dysplastic (“ND”), indefinite dysplasia (“IND”) or low-grade dysplasia (“LGD”) BE. There are approximately 4 million patients in the U.S. currently diagnosed with BE and approximately 415,000 patients annually undergo an endoscopic biopsy with a subsequent diagnosis of ND, IND or LGD BE, representing an estimated U.S. TAM of approximately $1 billion. In 2025, we expanded our capabilities in BE through the acquisition of Capsulomics, Inc., d/b/a Previse (“Previse”), which provides complementary methylation-based intellectual property and a non-endoscopic cell-collection technology.…