Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited disease associated with a marked increase in cancer susceptibility, especially cancer of the colorectum. It is one of the most common cancer predisposing syndromes affecting as many as one in 400 individuals in the Western World. Two (mismatch repair) genes (hMSH2 on chromosome 2p and hMLH1 on chromosome 3p) have recently been identified which appear to be involved in the development of cancer in most of the HNPCC families. Colorectal cancer in HNPCC differs from sporadic colorectal cancer by an early age of onset, a proclivity for the proximal colon, and an excess of synchronous and metachronous colorectal cancers. A variety of extracolonic tumors may be encountered in HNPCC, including cancers of the endometrium, stomach, small bowel, urinary tract (renal pelvis and ureter), biliary system and ovary. The diagnosis HNPCC is currently based upon the combined patient and family data. Future identification of HNPCC will be facilitated by the introduction of genetic markers. Identification of HNPCC families is extremely important, because periodic examination may prevent development of disease and death from cancer.