Atypical progressive multifocal leukoencephalopathy occurred in an 82-year-old man with long-standing chronic lymphocytic leukemia. The multifocal white matter lesions revealed demyelination and gliosis, relative preservation of axons and a prominent plasma cell infiltrate. Bizarre astrocytes were uncommon. There were no changes in the oligodendroglial nuclei and no inclusion bodies. Electron and immunohistofluorescence microscopy for papova virus were negative. In addition to this leukoencephalopathy a small primary cerebral lymphoma was present in the right occipital lobe. The tumor cells were plasmacytoid in appearance and their cytoplasm stained well with pyronin. They contained IgG by immunohistofluorescence microscopy. The neoplasm was considered an immunoblastic sarcoma (reticulum cell sarcoma) and thought to arise directly within foci of demyelination. Both disease processes, leukoencephalopathy and lymphoma, may have occurred on a background of immunosuppression.