Five cases of somatostatinoma are reported, four being primarily located in the pancreas and one in the duodenum. The diagnosis was based upon the histological and immunochemical characteristics of tumoral and metastatic tissue. A marked clinical heterogeneity was noted: one patient presented with gallstones, steatorrhea, and diabetes, two patients suffered from severe hypoglycemic attacks, and two cases were admitted for obstructive jaundice. This varying symptomatology was related to differences in the circulating levels of biologically active somatostatin and to a variable cellular composition of the tumor. In all cases, a basal and/or tolbutamide-induced hypersomatostatinemia was measured. It is concluded that the clinical and hormonal features of the earlier defined somatostatinoma syndrome are no requisite for the diagnosis of somatostatinoma; the analysis of plasma somatostatin immunoreactivity might lead to a higher detection rate of this endocrine tumor.