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Over the past 20 years, rates of early-onset colorectal cancer (eoCRC), defined as <50 years of age at diagnosis, have increased, with 16–25% associated with a pathogenic germline variant (PGV) resulting in a hereditary cancer syndrome. In the present study, we sought to further characterize PGVs observed in patients with eoCRC. We conducted a retrospective analysis of patients with a history of CRC referred for genetic counseling at Mayo Clinic Rochester between April 2019 and April 2022. Three hundred and three CRC patients were referred to medical genetics, including 124 with a history of eoCRC. Only 84 patients (68%) with eoCRC referred for genetic counseling completed genetic testing, with an average of 48 genes evaluated. PGVs were identified in 27.4% with eoCRC, including 8.3% with Lynch syndrome (LS). Other detected PGVs known to increase the risk of CRC included MUTYH (4.8%), CHEK2 (3.6%), APC, BMPR1A, and TP53 (1.3% each). Among those with aoCRC, 109 patients (61%) completed genetic testing, among which 88% had either a dMMR tumor, personal history of an additional LS malignancy, or family history of LS malignancy, with PGVs detected in 23% of patients. This study reinforces the importance for all patients with CRC, especially those with eoCRC, to undergo germline testing.