We describe a 68-year-old white woman who initially had symptoms of major depression and was admitted to a psychiatric hospital where she had electroconvulsive therapy. With failure of psychiatric treatment and subsequent rapidly progressive dementia, she had left frontal brain biopsy. The biopsy revealed spongiform changes, the hallmark of Creutzfeldt-Jakob disease (CJD). We report a case of sporadic CJD with unusual initial presentation of psychiatric symptoms.