Background: The increasing integration of somatic and germline testing into oncology practice allows physicians to target oncologic therapy and identify those with cancer predisposition. We explored the impact of a somatic assay (liquid biopsy, LB) on the identification of patients appropriate for germline genetic testing. Methods: We identified a cohort of diverse cancer patients with LB to assess for targetable somatic gene variants at LAC+USC Medical Center between 2016 and 2020 (n= 467). To enrich the cohort for variants that may reflect germline findings, we focused on the 46 patients (9.9%) who had at least one variant identified with a cell-free DNA (cfDNA) fraction of 25.00% or greater. Retrospective chart review extracted demographics and medical history with variables related to cancer history and treatment. LB variants were classified based on whether germline confirmation was indicated and the results of germline tests, when done, were reviewed. Results: Table summarizes the characteristics of the 46 patients identified to have at least one variant on LB in ≤ 25% of the cfDNA. The most frequently mutated genes on LB were TP53 (n=18, 39%), KRAS (n=11, 24%), APC (n=8, 17%), BRCA2 (n=7, 15%), PIK3CA (n=6, 13.0%), and BRCA1 (n=4, 9%). Seventeen patients (40%) were referred for genetic counseling and 13 (30%) underwent germline testing of whom 10 (77%) carried pathogenic variants (PV). All germline PV were concordant with LB variants identified. Four patients with PV BRCA2 on LB and confirmed to be germline, had lung or biliary tract diagnoses, which are not part of the typical BRCA-tumor spectrum. Thirty-three patients were not referred for genetic counseling, though 24 (72%) had LB-identified variants in cancer predisposition genes and 18 (54%) merited a genetics referral. Among patients with germline mutations, three (23%) had targeted therapy and two (15%) had preventive surgery to address second primary cancer risk. Among the 467 patients with LB results, there were an additional 13 patients (not included in the enriched group) known to have a cancer predisposition gene PV. Only two (15%) had findings on LB reports that suggested germline testing would be indicated. Conclusions: While the purpose of somatic testing is to identify targeted therapy, it can provide germline insight, especially for patients not typically referred for genetic assessment. Further education and guidance is needed to assure that this aspect of somatic testing is appreciated by oncology providers and acted upon.