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Introduction. Substance-related disorders are the most frequent comorbidity in schizophrenia. Concretely, alcohol is the most commonly consumed substance after tobacco. Patients with schizophrenia with this comorbidity have a worse clinical course and can develop serious neuropsychiatric complications. One of them, Marchiafava-Bignami disease (MBD) can be incorrectly diagnosed as a decompensation of their mental disorder. Methods. A case of a 51-year-old man, diagnosed with schizophrenia and alcohol use disorder is presented. He experienced acute neuropsychiatric symptoms for which schizophrenia decompensation was suspected. Based on his atypical symptoms and medical history, a brain imaging test was performed and MBD was diagnosed. Conclusions. MBD is an infrequent clinical entity that should be part of differential diagnosis in patients with alcohol abuse disorder experiencing atypical neuropsychiatric symptoms.