Historically, Lynch syndrome genes or PTEN have been linked to hereditary uterine cancer (UC); however, there is mounting evidence that other genes have a role and may offer novel clinical therapy options. UC patients were referred for extensive germline genetic testing, which included testing for Lynch syndrome, PTEN, and other cancer risk genes. Here, researchers analyzed the frequency of pathogenic germline variants (PGVs) found in these patients and their possible clinical significance. This retrospective study evaluated the prevalence of PGVs by syndrome type, patient age at testing, and self-reported ancestry among patients referred to a single clinical lab for germline genetic testing for an indication of uterine or endometrial cancer. Guidelines for clinical management, targeted treatments, and clinical trial eligibility were used to assess the potential clinical actionability of PGVs. PGVs were detected in 13.6% of the cohort (880/6490). Lynch syndrome genes (60.4%), PTEN (1.5%), and other cancer risk genes (38.1%; CHEK2, BRCA1/BRCA2) were the most common locations for PGVs. Patients under the age of 50 had comparable rates of PGV prevalence (15.1% and 13.2%, respectively). Nearly all PGVs (97.2%) were linked with guideline-recommended management, including cascade testing; 60.5% were associated with FDA-approved therapies, and 35.2% were linked with clinical trials. Germline testing for Lynch syndrome genes and PTEN, as well as testing just patients under the age of 50 at diagnosis, may miss a sizable proportion of UC patients who have actionable PGVs. Many UC patients and their at-risk relatives might benefit from universal, comprehensive genetic testing.