Total pancreatectomy (TP) is a treatment option for patients experiencing chronic pancreatitis (CP) refractory to medical management. Patients who are candidates for TP benefit from islet autotransplantation (IAT), which preserves available β-cell mass and thereby reduces the risk of brittle diabetes. Malignancy is an absolute contraindication for IAT to prevent the transplantation of occult malignant cells. We present the case of a patient with CP who was approved to undergo TP with IAT (TPIAT) but was intraoperatively discovered to have a pancreatic neuroendocrine tumor. The case illustrates a number of important surgical decision-making considerations for patients undergoing TPIAT and should help guide surgeons should they be presented with this clinical scenario. We stress the importance of vigilance for possible malignancy and to consider an intraoperative biopsy to further investigate unexpected findings that might represent an occult pancreatic malignancy in patients with CP undergoing TPIAT.