An intimate relationship between the exocrine and endocrine pancreas has been convincingly demonstrated in recent years. Animal experiments have shed some light into the complex dialog between the two tissues. This interaction is pronounced in diseases of the pancreas, especially in experimentally-induced and human pancreatic cancers. New evidence highlights the importance of intact islets in the development of exocrine pancreatic cancer. Although tumors arise from large and small ducts, invasive and malignant adenocarcinomas of ductal phenotype also derive from stem cells within islets. Development of cancer within islets explains the association between pancreatic cancer and impaired glucose tolerance or diabetes. Hence, the previous epidemiological studies suggesting that diabetes is a predisposing factor for pancreatic cancer are refuted. The available evidence suggests that pancreatic cancer in a large number of pancreatic cancer patients ultimately leads to diabetes, and that removal of the tumors improves or cures the diabetes. Both in the hamster pancreatic cancer model and in patients, the development of cancer is associated with elevated plasma levels of islet amyloid polypeptide, which may be used as a tumor marker.