Colorectal cancer (CRC) is the third most common malignancy in the United States. Advances in molecular biology have enhanced the understanding of colorectal carcinogenesis. Approximately 75% of CRCs are sporadic; the rest are hereditary or belong to a familial syndrome. Identification of familial forms of CRC have enabled the development of several models of carcinogenesis and made CRC a well-studied malignancy in terms of molecular pathogenesis. Pathways containing multiple mutations and genetic alterations that play a role in hereditary CRC pathogenesis have been elucidated. Many of the molecular changes seen in these pathways also are involved in the development of sporadic cancers.