The persistent hyperinsulinemic hypoglycemia may be caused either by a solitary tumor of the pancreas secreting excessive amount of insulin, known as insulinoma or, rarely, by nesidioblastosis. Nesidioblastosis is a rare cause of persistent hyperinsulinemic hypoglycemia in adults. The incidence of nesidioblastosis in adults is unknown, but it is generally thought to be very low. The β cell changes in adult nesidioblastosis suggest a dysregulation of the function of the cell. The cause of the functional dysregulation in adults is unknown. The pathogenesis of adult nesidioblastosis may be different from infantile congenital hyperinsulinism caused by a genetic effect. Histologically nesidioblastosis is almost always characterized by a proliferation of abnormal β cells throughout the entire pancreas. Clinically and biochemically , it is not possible to distinguish between diffuse nesidioblastosis and insulinoma. If all highly selective noninvasive imaging techiques fail to identify a tumor, selective arterial calcium stimulation testing should be performed. The final diagnosis relies on the histopathologic evaluation. The treatment of adult nesidioblastosis is surgical resection of the pancreas.