Colorectal Cancer (CRC) remains the third most common cancer affecting men and women in the United States. Approximately one-third of CRCs are diagnosed in individuals who have family members also affected with the disease. While the vast majority of colorectal neoplasms develop as a consequence of somatic genomic alterations arising in individual cells, approximately 5% of all CRCs arise in the setting of germline mutations in genes involved in key cellular processes. To date multiple genes have been implicated in single gene hereditary cancer syndromes, many of which are associated with increased risk for CRC, as well as other tumor types.