We present a patient with a clinically isolated syndrome suggestive of multiple sclerosis, who developed a full-blown picture of paranoid psychosis with suicidal attempt. Four new lesions were observed on brain MRI, one in the left and one in the right temporal lobe, one subcortically in the cingulate gyrus and one centrally in the tegmentum of the midbrain. The patient was treated with plasma exchange and recovered completely. Psychosis is not so rare symptom of multiple sclerosis as previously reported, and poses a major treatment challenge. A combination of lesions at strategic locations was a presumed mechanism of psychosis in this patient.