Medical disorders may be mistaken for a primary psychiatric disturbance because of prominent and commonly associated psychiatric or behavioral manifestations. The lack of recognition of the underlying medical condition precludes optimal treatment even though the psychiatric treatment might be appropriate for the symptoms, often manifesting as inadequate response or psychotropic treatment resistance. Deficiency of vitamin B12 has a well-established association with a wide variety of neurologic and psychiatric presentations includes slowed mentation, delirium, affective disorder, personality change, and acute or chronic psychosis. We present here a 41 year-old female patient who was previously hospitalized and then followed as schizophrenia without remission. During our current hospitalization, laboratory investigations confirmed very low serum B12 level and consequent megaloblastic anemia. She recovered dramatically with short term antipsychotic medication and intramuscular vitamin B12 supplementation. She remained asymptomatic and functionally independent at four months follow up. This case underscores the importance of considering vitamin B12 deficiency in the differential diagnosis of patients with schizophrenia.