Hereditary nonpolyposis colorectal carcinoma (HNPCC), or Lynch syndrome, is an autosomal dominant syndrome accounting for 5 to 10% of the total colorectal cancer population. Patients with this syndrome develop colorectal carcinoma at an early age, but disease onset can happen in all age groups. Usually the carcinomas are synchronous or metachronous, and most of them arise proximal to the splenic flexure. The prognosis is better than for the sporadic form of cancer, and there is increased risk for cancer development in certain extracolonic sites, such as the endometrium, ovary, stomach, small bowel, hepatobiliary tract, ureter, and renal pelvis. Most patients with HNPCC have a mutation in one of two DNA mismatch repair genes, hMSH2 or hMLH 1. More than 90% of colorectal carcinoma patients with hMSH2 or hMLH1 demonstrate high-frequency microsatellite instability (MSI-H). If a patient is suspected to belong to an HNPCC family, the first screening test should be immunohistochemistry for the detection of hMLH1 and hMSH2 proteins, and if it is indicative, it should be followed by genomic sequencing for the identification of mutations in the mismatch repair genes. Genetic counseling and surveillance for high risk HNPCC family members should begin at age 25. Surveillance includes annual colonoscopy of the entire large bowel, with fecal occult blood testing performed twice a year. Systematic surveillance and individually designed treatment of affected patients may help to detect cancers at an earlier stage and subsequently improve the prognosis of the disease further.