A 62-year-old man was given a diagnosis of small cell lung cancer, and received 6 courses of combination chemotherapy (PE therapy) composed of cisplatin (80 mg/m2, day 1) and etoposide (100 mg/m2, days 1, 2, 3). Multiple brain metastases were found, and whole brain irradiation (44 Gy) was given. Eleven months after radiotherapy, he suffered from dizziness and abnormal gait. Enhanced CT of the head showed slight enlargement of the lateral ventricles and markedly low density of the white matter, but no evidence of intracranial tumor involvement. A magnetic resonance scan (axial T2-weighted) showed symmetric extensive hyperintensity in the white matter. Treatment-related leukoencephalopathy caused by the PE therapy and whole brain irradiation was diagnosed. He was alive 8 months after the appearance of neurological symptoms, without recurrence of lung cancer. A search of the literature revealed no previous report of leukoencephalopathy related to PE therapy.