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A 14-year-old female spayed Golden Retriever was presented to the University of Florida's Veterinary Medical Center with history of lymphoplasmacytic gastroenteritis, intermittent vomiting, watery diarrhea, and weight loss for over a year. CBC, biochemical profile, and urinalysis were within reference intervals. Abdominal ultrasonographic examination revealed mesenteric and jejunal lymphadenopathy and hyperechoic hepatic nodules. Cytologic examination of the enlarged lymph nodes revealed loosely cohesive cells with moderate nuclear pleomorphism and rare punctate eosinophilic cytoplasmic granules. The cytologic interpretation was metastatic neuroendocrine neoplasia. On surgical exploration, a mass was detected in the right lobe of the pancreas. Histologic evaluation determined the mass to be an islet cell tumor. Approximately 98% of cells were positive by immunolabeling for pancreatic polypeptide (PP), and only rare cells were positive for insulin or somatostatin. All cells were negative for glucagon, gastrin, vasoactive intestinal polypeptide, protein gene product 9.5, synaptophysin, and chromogranins A and B. Pancreatic tumors that primarily produce PP are rare in dogs, and this is the first report of both the cytologic and histologic features of an islet cell tumor predominantly secreting PP. Clinical signs for these tumors are typically absent or nonspecific; signs may include watery diarrhea, as noted in this dog, although the diarrhea may have resulted from lymphoplasmacytic gastroenteritis. Additional case studies are needed to further characterize the cytomorphologic features and clinical presentation of PP-secreting islet cell tumor, or polypeptidoma, in dogs., (©2010 American Society for Veterinary Clinical Pathology.)