Previous survival studies suggested a better prognosis of hereditary nonpolyposis colorectal cancer (HNPCC) patients compared with the sporadic counterpart. In the present study we evaluated the clinical outcome of HNPCC patients with respect to that of patients with colorectal cancer recorded in a population-based cancer registry. We assessed survival of 85 colorectal cancer patients from 24 unrelated families defined as having HNPCC according to the criteria of the International Collaborative Group, for whom adequate information on subject- and tumor-related parameters and a 5-year follow-up (cancer diagnosis from 1980-1989) were available. Three hundred and seventy-seven colorectal cancer patients, registered from 1984-1986, with a 5-year follow-up, were used for comparison. Colorectal cancer-specific 5-year survival rates were 55.2% and 42.5% for HNPCC and non-HNPCC, respectively. Using Cox regression analysis, tumor staging and location were independently associated with survival, whereas HNPCC diagnosis was not. Stage II HNPCC cases exhibited a better prognosis than non-HNPCC patients. By Cox regression analysis, none of the variables were significantly related to survival. Both overall and stage II HNPCC cases showed a survival advantage in comparison with non-HNPCC patients. However, the difference disappeared when clinical and pathological variables were controlled for with a Cox regression analysis.