Between 1971 and 2002, 80 patients underwent surgery for insulinoma at the Department of General and Endocrine Surgery of the Lille University Hospitals. The present report deals with 13 patients with proven multiple endocrine neoplasia type I (MEN I) or supposed genetic-related insulinomas. This entity differs from spontaneous insulinoma by the presence of multiple foci in the pancreas. Enucleation is not advised in this setting due to the strong likelihood of persistence or recurrence. Various studies suggest different strategies for preoperative localization and surgical approach. We analyzed retrospectively the surgical strategy proposed by the A.F.C.E. and G.E.N.E.M. The purpose of this study was to validate the strategy, integrate the contribution of genotypic diagnosis, simplify preoperative imaging studies, and re-evaluate the value of intraoperative baseline secretin-stimulated insulin measurements. We recommend preoperative endoscopic ultrasonography of the pancreatic head only and routine left pancreatectomy with enucleation of cephalic tumors under intraoperative hormone monitoring. Preoperative invasive localization studies are proposed only if the endoscopic ultrasonography is negative for the pancreatic head. Intraoperative secretin stimulation test can be useful in difficult cases, especially with concurrent nesidioblastosis or in case of secondary surgery. All but one of the 13 patients achieved long-term cure with this strategy.