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The embryogenesis of the pancreas suggests the existence of a common stem cell progenitor of the four islet cell types (insulin, glucagon, somatostatin, and pancreatic polypeptide). We investigated whether neoplastic islet tumors express multiple hormone-specific cellular phenotypes of the islets. By analyses of RNA transcripts and immunoreactive peptides in four human insulinomas and one glucagonoma, we found that the insulin, somatostatin, and glucagon genes were coexpressed in all tumors. The expression of the three hormone genes in a lymph node metastasis of a glucagonoma reduced the possibility that contamination of tumor tissue by normal islets occurred. These observations lend further support to the hypothesis of the multipotentiality of neoplastic islet cells for the expression of genes encoding several different islet hormones.