A 14-year-old spayed female domestic shorthair cat was evaluated for weakness, lethargy, decreased appetite, diarrhea, weight loss, and seizures. On physical examination, the cat appeared disoriented and had an inconsistent menace response. An insulinoma was diagnosed on the basis of normal serum insulin activity in conjunction with profound hypoglycemia and histologic examination (with immunohistochemical staining for chromogranin A and insulin) of a pancreatic mass that was removed surgically. Blood glucose concentration was within reference limits after surgery. However, neurologic abnormalities persisted, and the cat was euthanatized. Chronic hypoglycemia, associated with insulinomas, can cause irreversible neuronal changes in cats; therefore, rapid diagnosis and treatment of hypoglycemic conditions are of critical importance.