The etiology of pancreatic cancer remains elusive. Recent attention has been given to host factors, as evidenced by the recognition of familial aggregations of this disease and its association with several hereditary cancer-prone disorders. We have investigated a remarkable family wherein pancreatic cancer has been documented through three generations, including progeny from two of the progenitor's three marriages. The protocol involved a search for documentation of cancer of all anatomic sites. We did not find any pattern of extrapancreatic cancer occurrences, and age at onset of pancreatic cancer corresponded to population expectations. The recognition of patients at high risk for pancreatic cancer should lead to research into potential environmental factors interacting with host susceptibility for elucidation of etiology and for earlier diagnosis.