We report the case of a 24-year-old female patient who initially developed a neuroleptic malignant syndrome after haloperidol exposure and experienced 6 years later a serotonin syndrome after repeated fluoxetine exposure. The patient did not respond to symptomatic treatment and died in this latter episode. At necropsy, no gross or microscopic changes were seen with conventional histological stains, and immunohistochemical stains were negative. This is the first clinicopathologic case of a patient who experienced both neuroleptic malignant and serotonin syndromes. We speculate that this case argue in favor that both syndromes share some fundamental pathogenetic mechanisms.