Multiple endocrine neoplasia 1 (MEN1) is a rare autosomal-dominant disorder characterized by the development of tumors in endocrine glands and the duodenum. Duodenal gastrinomas (gastrin-secreting neuroendocrine tumors) are frequently associated with MEN1 mutations, but their natural history is poorly understood. This limits the development of new therapies for serious complications such as ulcers and severe diarrhea caused by hypergastrinemia in these individuals. New findings in this issue of Gastroenterology by Sundaresan et al1 have the potential to overcome this roadblock by providing important new insight into the mechanisms that produce MEN1-associated duodenal gastrinomas.