A 50-year-old man with Burkitt lymphoma developed leukoencephalopathy after a course of combined prophylactic chemotherapy including intrathecal methotrexate for Burkitt lymphoma. Neuroimaging studies were minimally abnormal upon symptom onset, but three days later demonstrated severe, bilateral, confluent, symmetric deep white matter diffusion restriction in areas still nearly normal on the fluid attenuated inversion recovery (FLAIR) images. Chemotherapy was the most likely etiology but the differential diagnosis would include progressive multifocal leukoencephalopathy and brain involvement by tumor. Pathological confirmation in cases of chemotherapy induced leukoencephalopathy is rare because patients often survive. In this case pathologic confirmation of the diagnosis at autopsy was possible within 9 days of onset of severe diffusion weighted imaging abnormalities. In fatal cases of disseminated necrotizing leukoencephalopathy (DNL) autopsy frequently reveals severe changes including necrosis. This case showed much milder changes included intracellular and extracellular edema, axonal retraction bulbs, gliosis and macrophage infiltration. This could represent a potentially reversible, early form of chemotherapy associated leukoencephalopathy. The term acute disseminated leukoencephalopathy (ADL) describes the MRI and pathologic appearance of this case and distinguishes such cases from disseminated necrotizing leukoencephalopathy (DNL).