A seventy-four year old man with primary adenocarcinoma of the colon and hepatic metastases was found to have severe hypoglycemia. A recently developed test using glucagon excluded the possibility of hyperinsulinism and deficient hepatic storage of glycogen as mechanisms for hypoglycemia. Pancreatic islet alpha cell granules were markedly decreased. Twelve similar cases of neoplasms of the gastrointestinal tract with dependent hypoglycemia have been found in the literature. Mechanisms proposed to explain this hypoglycemia are numerous and no single mechanism can explain the oncogenic hypoglycemia in all reported cases.