A Case is presented of a 23-year-old woman with progressive onset of paranoid psychosis and catatonia, who was ultimately found to have both vitamin B12 deficiency and a family history of bipolar disorder. The patient was initially diagnosed with schizophrenia and treated with the antipsychotic medication ziprasidone. Her condition rapidly worsened to a state consistent with either neuroleptic malignant syndrome or malignant catatonia. Work-up then revealed vitamin B12 deficiency and a family history of bipolar disorder. Her symptoms improved rapidly but partially with benzodiazepines and electrocon-vulsive therapy, and completely with addition of valproic acid, vitamin B12 replacement, and re-introduction of antipsychotic medication in the form of olanzapine. The authors discuss the differential diagnosis of catatonia as reflecting a high likelihood of underlying mood disorder; the evaluation and management of malignant catatonia and malignant neuroleptic syndrome; and the role of vitamin B12 deficiency in precipitating psychotic symptoms. The case also illustrates the problems of diagnosing and managing a multifactorial disorder with psychiatric, general medical, and perhaps iatrogenic components.