Gastrinoma is the most common functional neuroendocrine tumor of the duodenal/pancreas in MEN-1. Between 30% and 60% of patients with MEN-1 develop gastrinoma, and 20–25% of gastrinomas are associated with the familial MEN-1 syndrome. The majority of primary gastrinomas are located in the duodenal wall. Two/thirds of the primary duodenal gastrinomas are multifocal and one third are solitary in MEN-1. The proportion of primary gastrinoma located in the duodenal is slightly higher for MEN-1 patients compared to sporadic gastrinoma. There were still 5–10% of patients with MEN-1 who have primary pancreatic gastrinoma. Although it was initially felt that metastatic gastrinoma was the leading cause of death in MEN-1, it has been recognized that these tumors are more indolent than sporadic gastrinoma and rarely cause death due to the spread of malignancy. The leading cause of death in MEN-1 is now considered metastatic higher grade nonfunctional pancreas neuroendocrine tumor. Because of the multifocal duodenal disease the most reliable surgical procedure to cure gastrinoma in MEN-1 is a classic Whipple or pancreatico-duodenectomy. With the development of potent antacid medications such as proton pump inhibitors the controversy is whether patients with a relatively indolent tumor with slow progression and minimal chance of mortality in which the symptoms can be controlled medically should undergo a pancreatico-duodenectomy. For experienced surgeons with low complication rates following pancreatico-duodenectomy and in selected patients with no comorbidities facing lifelong treatment with antacid medication, it is appropriate to consider this operation which will potentially be curative in up to 75% of patients (Table 34.1).