Marchiafava-Bignami disease (MBD) was diagnosed in a 56-year-old man. Spin-echo (SE) magnetic resonance imaging (MRI) at the acute phase showed normal signal areas in the central layer of the corpus callosum (CC), although the intensity of these areas revealed abnormal hyperintensity on fluid attenuated inversion recovery (FLAIR). On follow-up SE MRI at the late phase, the central layer of the CC showed fluid-like intensity. On FLAIR MRI, the lesions of the CC turned into hypointense cores surrounded by hyperintense rims indicating central necrosis and peripheral demyelination. Degenerative changes of the CC in MBD were clearly demonstrated by FLAIR MRI.