A 12-year-old female Irish Setter was examined because of recurrent episodes of hindlimb weakness. The dog was not ataxic, but had generalized muscular atrophy, decreased patellar reflexes, and slow proprioception. Blood glucose content was low (32 mg/dl) and the amended insulin-glucose ratio was high (9,600). Electromyographic studies showed evidence of polyneuropathy. The diagnosis was functional islet B-cell tumor with peripheral neuropathy. Exploratory laparotomy was performed. Widespread metastases were observed and the dog was euthanatized because of the poor prognosis. The dog was necropsied and the diagnosis was confirmed on the basis of microscopic findings.