Lynch syndrome, now referred to as hereditary nonpolyposis colorectal cancer (HNPCC), was first identified in a family in 1895. In 1966, Henry Lynch discovered a series of families with colon and other cancers in Nebraska. Today, the evidence demonstrates that HNPCC is associated with germline pathogenic variants in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes, which are mismatch repair (MMR) genes.