Pancreatic cancer in many patients is associated with altered glucose metabolism and abnormalities in pancreatic islet hormones at serum and tissue levels. Our previous studies have indicated a tendency of islet cells to differentiate toward ductal cell lineage, but the specificity of these findings for pancreatic cancer was not investigated. In the present study, we examined the immunoreactivity of pancreatic islets to antibodies against tumor-associated antigens DU-PAN-2, TAG-72 and CA19-9 in tissues from the normal pancreas, chronic pancreatitis and pancreatic cancer. Although no immunoreactive islet cells were found in the 12 normal pancreases and 20 chronic pancreatitis patients, 25 of 37 pancreatic cancer tissues showed the expression of these antigens, primarily CA19-9 and TAG-72, where the number of immunoreactive cells varied considerably from case to case. In 4 cases over 50% and in 2 of them more than 75% of the islets showed positive staining of 60-70% of islet cells within each islet. The presence of intrainsular ductular structures expressing the same antigen as the surrounding islet cells suggested transformation of antigen expressing islet cells to ductal cells. All but four islets were within or around the cancer favoring the notion that factors produced by cancer cells are responsible for the altered islet cell differentiation.