In addition to the well-recognized syndromes described (FAP, HNPCC) clusters of colorectal cancers occur in families much more often than would be expected by chance. This familial clustering in about 10-20% of colorectal cancers has implications for screening because the immediate family members of a patient with apparent sporadic colorectal cancer have a twofold to threefold increased risk of the disease. The magnitude of the risk depends on the age at diagnosis of the index case, the degree of kinship of the index case to the at-risk case, and the number of affected relatives. In addition to screening the easily identifiable high-risk groups such as FAP and HNPCC, care should be taken to recognize intermediate-risk patients and to provide them with appropriate screening recommendations. Because the molecular basis and the natural history of these intermediate-risk patients are largely unknown, screening recommendations are as yet more empirical. If a person has a first degree relative with colon cancer, average risk colon cancer screening is recommended, but starting at age 40 years. The decreased age is given because the risk at age 40 for those with an affected first-degree relative is similar to the risk at age 50 for the general population. An individual with two first-degree relatives affected with colon cancer or one first-degree relative diagnosed under the age of 60 y should have colonoscopy beginning at age 40, or 10 years younger than the earliest case in the family. Colonoscopy should be repeated every five years if negative. An even stronger family history of colon cancer syndromes of colon cancer should suggest the consideration of one of the inherited syndromes.