Epi proColon® is a blood-based colorectal cancer (CRC) screening test that presents a convenient, non-invasive option for CRC screening in average-risk adults aged ≥ 50 years who are otherwise non-compliant to guideline-recommended screening programs. The Epi proColon test involves the use of a real-time PCR assay to detect methylated Sept9 DNA (a biomarker for CRC) in plasma derived from a whole blood sample. Epi proColon generally performed well in prospective clinical trials, having non-inferior sensitivity for detecting CRC compared with a fecal immunochemical test (FIT). Microsimulation modeling supports annual Epi proColon testing, as for FIT. Although the Epi proColon test specificity is lower than that of a FIT, the Epi proColon test may be useful for improving participation and compliance in CRC screening, as evidenced in a small randomized controlled clinical trial which showed that uptake of an offer of an Epi proColon blood test was significantly higher than that for a FIT in subjects who were overdue for CRC screening.