This case reports a middle-aged male patient presented with involuntary limb tremors as the initial symptom. The patient had a history of chronic alcoholism and experienced an upper respiratory tract infection one week prior to symptom onset. Cranial MRI revealed the characteristic of "sandwich sign" in the corpus callosum. Based on the patient's clinical symptoms, physical signs, and ancillary investigations, a diagnosis of primary Marchiaffava-Bignami disease (MBD) was established. By reviewing the pathophysiological mechanism underlying this specific "sandwich sign" imaging finding, this report explores the diagnostic approach for differentiating the "sandwich sign" of the corpus callosum.