The subacute development of Marchiafava-Bignami disease (MBD) is reported in a 60-year-old patient from Southern Germany with a history of chronic alcoholism and severe malnutrition. Computed tomography scans showed progressive white matter destruction over a period of 8 months, ranging from diffuse hypodensities to well-delineated, strongly hypodense areas in the central hemispheric white matter of both frontal and parietal lobes and in the corpus callosum. Autopsy revealed an identical pattern of demyelinated, partially necrotic lesions in addition to small cystic necroses in the genu corporis callosi. The temporal evolution of MBD, criteria for early diagnosis and pathogenetic aspects are discussed.