Our results support the notion that early-onset BC in HNPCC may be due to mutations in other genes, such as BRCA2, and that early-onset CRC in BRCA1/2 may be due to mutations in MMR genes, such as MSH2. This report describes the phenotype of the first two individuals in whom truncating mutations in both genes have been identified. Here, MSH2 is linked to hereditary nonpolyposis colon cancer.