The corpus callosum plays a vital role in brain function. In particular, in the trunk of the corpus callosum, in the course of various diseases, there may be temporary, reversible changes (reversible splenial lesion syndrome (RESLES)), as well as partially reversible and irreversible changes. This article discusses the differentiation of RESLES and other conditions with changes in the corpus callosum lobe, as well as the accompanying clinical symptoms. Moreover, a case report of a patient in whom the above changes appeared in the nuclear magnetic resonance (NMR) image is presented. A 20-year-old patient with the diagnosis of Ehlers–Danlos syndrome type VI was admitted to the psychiatric ward in an emergency because of psychomotor agitation, refusal to take food and fluids, delusional statements with a message, grandeur, and auditory hallucinations. In the performed magnetic resonance imaging (MRI) of the brain, the corpus callosum non-characteristic in T2-weighted images revealed a hyperintensive area, which was significantly hyperintensive in diffusion magnetic resonance (DWI) sequences and in apparent diffusion coefficient (ADC) sequences with reduced signal intensity and no signs of bleeding. The hypothesis of subacute ischemic stroke of the corpus callosum was presented. In the control MRI of the brain, changes in the corpus callosum completely regressed, thus excluding an ischemic etiology and favoring the diagnosis of RESLES. During hospitalization, the patient experienced significant fluctuations in mental status, with the dominant symptoms typical of the paranoid syndrome in the form of disturbances in the course and structure of thinking and perception, and a clear and stable improvement was obtained after the administration of long-acting intramuscular olanzapine. Taking into account the clinical and radiological picture, the age of the episode, the rapidity of the disease development, the persistence of its clinical symptoms after the withdrawal of radiological changes in the brain NMR image, as well as the significant improvement in the clinical condition after the introduction of antipsychotic drugs, the final diagnosis was made of schizophrenia.