Marchiafava-Bignami disease (MBD) is a rare alcohol-associated disorder characterized by demyelination and necrosis of the corpus callosum. We herein present the case of a 56-year-old man with chronic alcoholism who was admitted to our hospital in a coma without focal or lateralizing neurological signs. MRI revealed a callosal lesion consistent with MBD and additional bifrontal linear cortical lesions. The callosal lesion completely disappeared with intravenous administration of high-dose multivitamins and corticosteroids, although the patient remained in a vegetative state. This case further supports the notion that cortical involvement in patients with MBD is a predictor of a poor prognosis.