Colon cancer remains the third leading cause of death due to cancer in the US, where it affected more than 145,000 individuals in 2005. Up to 30% of these cases exhibit familial clustering, which means that tens of thousands of individuals have a disease with a potentially definable genetic component. Approximately 3-5% of colon cancers are associated with high-risk, inherited colon cancer syndromes. Identification of the genes that cause these colon cancer syndromes, coupled with additional insights into their clinical course, has led to the development of specific management guidelines--and genetic tests--that can diagnose these familial disorders. These guidelines can be life-saving, not only for the affected patient, but also for their family members.