The best approach for screening patients hinges on the number, degree, and age of relatives diagnosed with colorectal cancer (CRC) or adenomatous polyps (AP). Screening should begin at 40 years of age for patients with a family history of CRC or AP in at least 1 first-degree relative or CRC in at least 2 second-degree relatives. Patients at highest risk-who have 1 first-degree relative diagnosed with CRC or AP before 60 years of age or multiple first-degree relatives diagnosed at any age-should begin screening with colonoscopy at 40 years of age or 10 years younger than the earliest affected relative and undergo a repeat colonoscopy every 5 years. Patients who have a first-degree relative diagnosed with CRC or AP after 60 years of age or 2 or more second-degree relatives with CRC should start screening at 40 years of age, with routine options and follow-up intervals. (Routine options and follow-up intervals include any of the following 3 regimens: annual high-sensitivity fecal occult blood testing, sigmoidoscopy every 5 years combined with high-sensitivity fecal occult blood testing every 3 years, or screening colonoscopy every 10 years.).