Abstract Background: Blood based tests for multi-cancer early detection (MCED) are being developed to facilitate the earlier detection of various cancer types. The Detecting cancers Earlier Through Elective mutation-based blood Collection and Testing (DETECT-A) study evaluated the CancerSEEK MCED test, an early version of the Exact Sciences MCED test in development, in 9,911 women, age 65-75, without previous history of cancer (Lennon et al., Science 2020). The degree to which MCED testing will facilitate detection of precancerous conditions or incidental findings is unclear. Here we focus on DETECT-A participants who had pre-cancerous conditions diagnosed during a diagnostic work-up for a positive CancerSEEK MCED test. Methods: In a post-hoc analysis, we report on the detection of precancerous conditions consequent to CancerSEEK MCED testing and follow-up. Electronic health records were reviewed for diagnostic procedures performed, details of premalignant and cancer diagnoses, and vital status. Results: In three individuals, mutations in PIK3CA, TP53, or KRAS genes led to a positive CancerSEEK MCED test result. The prescribed imaging protocol using 2-deoxy-2[fluorine-18] fluoro-D-glucose positron emission tomography-computed tomography (18-FDG PET-CT), revealed a 10.3 × 9.8 × 7.8(cm) ovarian mucinous cystadenoma, a 0.8 cm appendiceal mucinous neoplasm, and 3 colonic polyps displaying high-grade dysplasia. All three participants were diagnosed with clinically significant pre-cancerous lesions, subsequently underwent surgical treatment, and remain alive and cancer-free as of February 2023 (Table 1). Conclusion: The diagnostic evaluation of a positive MCED test may occasionally reveal clinically significant pre-cancerous conditions amenable to interventions. The frequency of such findings and their clinical impact warrants further study. Citation Format: Omair A. Choudhry, Angana Kharge, Seema P. Rego, Paul Z. Elias, Adam H. Buchanan, Anne Marie Lennon, Nickolas Papadopoulos, Frank Diehl, Tomasz M. Beer. Case report: DETECT-A participants with pre-malignant conditions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2449.