Two cases of pancreatic islet cell adenoma are described, one in a newborn female, the other in a 6-year-old girl, bringing to 27 the number of reported cases in children. Apart from the demonstration of persistent hypoglycemia, extensive biochemical studies in the older child revealed normal function of pancreas, other endocrine glands, and liver. Partial remission with ACTH therapy was successful for some months, following which, there was progressive deterioration including the appearance of convulsions during normal glycemia but presumably reflecting encephalopathy induced by the chronic hypoglycemia. Cure with disappearance of the encephalopathy was achieved by total pancreatectomy, at the expense of diabetes mellitus and external pancreatic insufficiencies each of which was satisfactorily controlled by appropriate replacement therapy. This case and other recorded ones illustrate the unreliability of biochemical tests in establishing the diagnosis of pancreatic adenoma. It must be suspected after elimination of all other known specific etiologies, then differentiated from idiopathic functional hypoglycemia by the demonstration of progressive resistance of organic hyperinsulinism to ACTH therapy, and finally confirmed by subtotal or even total pancreatectomy with meticulous search for adenoma on serial section of the gland. Two cases of pancreatic islet cell adenoma are described, one in a newborn female, the other in a 6-year-old girl, bringing to 27 the number of reported cases in children. Apart from the demonstration of persistent hypoglycemia, extensive biochemical studies in the older child revealed normal function of pancreas, other endocrine glands, and liver. Partial remission with ACTH therapy was successful for some months, following which, there was progressive deterioration including the appearance of convulsions during normal glycemia but presumably reflecting encephalopathy induced by the chronic hypoglycemia. Cure with disappearance of the encephalopathy was achieved by total pancreatectomy, at the expense of diabetes mellitus and external pancreatic insufficiencies each of which was satisfactorily controlled by appropriate replacement therapy. This case and other recorded ones illustrate the unreliability of biochemical tests in establishing the diagnosis of pancreatic adenoma. It must be suspected after elimination of all other known specific etiologies, then differentiated from idiopathic functional hypoglycemia by the demonstration of progressive resistance of organic hyperinsulinism to ACTH therapy, and finally confirmed by subtotal or even total pancreatectomy with meticulous search for adenoma on serial section of the gland.