A 7.5-year-old captive born Savannah monitor, Varanus exanthematicus, presented with lethargy, anorexia, constipation, and narcolepsy-like behavior. Plasma biochemical analysis demonstrated mildly elevated liver enzymes, hypercalcemia, and hypoproteinemia. Coelomic ultrasound revealed multiple echolucent and rare echogenic round hepatic structures. Diagnostic coelioscopy was attempted but limited by anesthetic complications and varanid anatomy. Although it could not be confirmed during surgery, clinical signs and blood work supported hepatic disease. Because of progression and severity of clinical signs, the monitor was humanely euthanized. Further histopathologic evaluation revealed a pancreatic islet cell tumor with hepatic metastases and multifocal hepatic cholangiocarcinomas. Insulin immunoassay values were used post-mortem in this case and may be useful for diagnosis of insulinoma in reptiles. To the authors' knowledge, this is the first report of a reptile with functional islet cell neoplasia that demonstrated clinical illness and elevated insulin levels.