Leigh's disease (subacute necrotizing encephalomyelopathy) is a progressive neurological disorder caused by mitochondrial dysfunction that occurs primarily in infancy and childhood and only rarely in adulthood. We report a 40-year-old-woman, who had been diagnosed as having multiple sclerosis (MS) at age 38 after developing several episodes of transient diplopia, ataxia, and facial weakness on the right side. She was admitted to our hospital due to stupor, nystagmus, diplopia, and fever. Neurological findings included stupor, ataxic speech, nystagmus, diplopia on the right horizontal gaze, hyperreflexia on the dominant right side, bilateral extensor plantar responses, hypoesthesia on the left side of the face and extremities, hypermetria on the extremities, the presence of Romberg's sign, and ataxic gait. Brain MRI showed abnormal lesions in the peri-third ventricle, the periaqueductal gray matter of the midbrain, the hypothalamus, and the pontine tegmenta on the right side. The cerebrospinal fluid (CSF) contained 96 mg/dl protein and increased IgG. Serum and CSF lactic acid and pyruvate levels were increased. Aerobic testing was positive; muscle biopsy and mitochondrial DNA analysis were negative. ^<123>I-BMIPP myocardial images detected reduced uptake in the anterior-wall and apical portion. The myocardial biopsy revealed degeneration of myocardial fibers and mitochondrial abnormalities, such as increased size and abnormal inclusions. Therefore, adult Leigh's disease was diagnosed. The patient died unexpectedly due to acute respiratory failure at age 42. An autopsy was not performed. In patients with MS-like symptoms and MRI findings in the midbrain, brain stem, and basal ganglia, the possibility of adult Leigh's disease should be considered.