Colorectal cancer (CRC) screening is a cost-effective approach to reduce morbidity, mortality, and prevalence of CRC in populations. Current recommendations for asymptomatic populations begin screening at age 50 years, after which ~95% of cancers occur. Determinants that modify timing and frequency for screening include: personal/family history of adenomas or CRC, age of onset of lesions, and presence or potential to harbor high-risk conditions like inflammatory bowel disease (IBD), familial adenomatous polyposis (FAP), or Lynch syndrome. Although race, like family history, is heritable, it has not engendered inclusion in systematic screening recommendations despite multiple studies demonstrating disparity in the incidence and mortality from CRC, and the potential for targeted screening to reduce disparity. African Americans, when compared to Caucasians, have lower CRC screening utilization, younger presentation for CRC, higher CRC prevalence at all ages, and higher proportion of CRCs before age 50 years (~11 vs. 5%); are less likely to transmit personal/family history of adenomas or CRC that may change screening age; show excess of high-risk proximal adenomas, matched with 7-15% excess right-sided CRCs that lack microsatellite instability; show higher frequencies of high-risk adenomas for every age decile; and demonstrate genetic biomarkers associated with metastasis. These epidemiological and biological parameters put African Americans at higher risk from CRC irrespective of socioeconomic issues, like IBD, FAP, and Lynch patients. Including race as a factor in national CRC screening guidelines and commencing screening at an age earlier than 50 years seems rational based on the natural history and aggressive behavior in this population.