Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) refers to autosomal dominant predisposition to colorectal, endometrial, and a spectrum of other cancers. The syndrome is due to heterozygous germ line mutations in one of the mismatch repair genes MLH1, MSH2, MSH6, and PMS2. Amsterdam I and II criteria for clinical diagnosis and Bethesda guidelines for molecular testing of suspected patients usually point out additional families in which there is no evidence of mismatch repair deficiency even after screening by microsatellite instability analysis and/or immunohistochemistry for mismatch repair proteins. Hence, the term "Lynch syndrome" should be restricted to those families with germ line mutations in one of the mismatch repair genes. Familial colorectal tumors with no evidence of mismatch repair deficiency were shown to be clinically and molecularly distinct from classical Lynch syndrome tumors and, therefore, were designated "familial colorectal cancer type X" (FCC-X). The predisposing gene(s) to FCC-X is as yet unknown, but extensive research is currently underway to delineate its etiology. Given the above distinctions, the term hereditary nonpolyposis colorectal cancer (HNPCC), which was formerly used to refer to clinically diagnosed colorectal cancer families that might or might not have mismatch repair deficiency, is being replaced by one of the more informative names: Lynch syndrome and FCC-X.