Metallothioneins (MTs) are intracellular proteins that bind to metal ions and are involved in heavy metal homeostasis and detoxification. Pancreatic islets were shown to be positive for zinc-containing matrix metalloproteinase-2 and -9 by immunocytochemical staining. The immunolocalization of matrix metalloproteinases in pancreatic islets prompted us to study further the link between zinc and MT in 34 cases of pancreatic endocrine neoplasms, including insulinomas, glucagonomas, gastrinomas, pancreatic polypeptide-omas, and non-functioning endocrine neoplasms. Four types of islet cells were found to be positive for MT, whereas pancreatic endocrine neoplasms mostly were either weakly positive or negative for MT. The presence of MT in normal islet cells and pancreatic endocrine neoplasms is consistent with the notion that MTs modulate zinc homeostasis and metabolism in pancreatic islet cells and pancreatic endocrine neoplasms as those tissues contain zinc-containing matrix metalloproteinases.