Patients affected by chronic pancreatitis were followed between 1970 and 1984 in a study set up to evaluate the natural history of the disease. The study population included 172 consecutive patients diagnosed as having chronic pancreatitis in the Gastroenterology Unit of the S. Giovanni Battista Hospital in Torino, Italy. Of them, 23 were found to be affected by cancer during the 14-year follow-up period. The incidence calculated using the person-year method was compared with data from the General Population Cancer Registry of Piemonte Region. The age-specific relative risks of cancer were increased manifold. Sex- and age-specific relative risks were markedly increased for liver, tongue, lip, and rectum tumors in males, and for liver, bone, and breast tumors in females. Selection bias did not seem to be an adequate explanation of this association. Survival curves were plotted by the estimation methods of Cutler-Ederer with year intervals for the complete study population and for the different type of cancer. Known risk factors and indicators for the expected tumors were evaluated by the Cox Proportional Hazard Regression Model. The incidence of cancer increases significantly with age but not with smoking, alcohol use, and diabetes. Our epidemiological study suggests an increased risk of pancreatic as well as extrapancreatic cancer in patients with chronic pancreatitis compared with the general population. Cancer seems to be a main determinant in the natural history of the disease.