We report multiple system atrophy (MSA) of 14 years' duration in a 75-year-old woman. Postmortem examination revealed pathological changes typical of MSA. Furthermore, neuronal loss with astrocytosis in the primary motor and premotor cortices, especially in the fifth and sixth layers, and extensive myelin and axonal loss in the frontal and parietal white matter were evident. There were numerous ubiquitin-positive oligodendroglial inclusions, which are characteristic of MSA, in these cortical and white matter lesions. These findings suggest that the motor cortical areas and cerebral white matter are sites of significant involvement in the MSA disease process and that inclusion-bearing oligodendroglial alterations contribute to the white matter degeneration.