A 3-year-old male grey collie and 4-year-old female grey collie were part of a cyclic hematopoiesis study. Both dogs had experienced numerous bacterial infections, and both dogs were receiving various treatment regimens, including lithium and hematopoietic growth factors, to control the cyclic hematopoiesis. The first dog was presented in acute collapse and had a rapid clinical course. The second dog was presented with pyrexia and subsequently developed anorexia, disorientation, tremors, mild diarrhea, and bruising at venipuncture sites. Postmortem examination revealed pancreatic adenocarcinoma with metastasis in both cases. Pancreatic adenocarcinoma is a rare neoplasm in dogs. The incidence of pancreatic adenocarcinoma noted in this report is more than 150 times that previously reported in dogs. The cause of the increased incidence of pancreatic malignancy in these grey collies is unknown; possible factors include chronic inflammation or infections, chronic drug therapy, or genetic predisposition. Development of an uncommon neoplasm in two young grey collies may offer an opportunity to study the mechanisms of carcinogenesis.