This report describes an immunocompetent patient with memory loss and motor abnormalities whose magnetic resonance images demonstrated multiple enhancing white matter lesions, including one that was cystic, suggestive of metastatic tumors or abscesses. Neuropathological evaluation at biopsy and subsequent autopsy revealed progressive multifocal leukoencephalopathy. Magnetic resonance evidence of enhancement and cystic changes are rare findings in progressive multifocal leukoencephalopathy, but should be considered in the differential diagnosis, especially in patients without evidence for primary malignancy or infection.