Pancreatic neuroendocrine tumors (PNETs) have an incidence of approximately 1 per 100,000 individuals per year, and account for 1–2% of all pancreatic tumors. The annual incidence in the United States is about 3.65 per 100,000 population. Although they may manifest at any age, they most often occur in the fourth to sixth decades of life. Most PNETs are sporadic, but they can be associated with hereditary endocrinopathies involving loss of a possible tumor-suppressor gene, including Multiple Endocrine Neoplasia Type 1 (MEN1), Von Hippel Lindau (VHL) syndrome, Neurofibromatosis Type I (NF1), and Tuberous sclerosis. Approximately 80–100% of the patients with MEN1, up to 20% of the patients with VHL, 10% of the patients with NF1, and 1% of the patients with tuberous sclerosis will develop a PNET. Of these, MEN1 is the most common. It is characterized by pancreatic, pituitary, and parathyroid malignancies. MEN syndrome is present in 20–30% of patients with Zollinger–Ellison Syndrome (ZES), in whom gastrinomas tend to be multifocal, less aggressive, and located submucosally in the duodenum.