Postoperative onset of acute major depression in a patient with no previous history of psychiatric disorder is highly unexpected after skull base surgery.A 38-year-old woman with no previous physical or mental illness presented with a 3-month history of left ear pain, short-term memory disturbance, and motor dysphasia. Magnetic resonance imaging revealed a large extraaxial tumor in the left middle fossa. Left temporal craniotomy was performed, achieving complete tumor resection. The patient showed signs of confusion, disorientation, and severe depression 3 days after the surgery. She developed insomnia and auditory hallucinations along with expressed suicidal ideation, then deteriorated rapidly, necessitating a transfer to a psychiatric unit. In spite of the intensive treatment with antidepressive and antipsychotic medications, she continued to have prolonged psychotic symptoms and depression for several months after surgery.Although the incidence is rare, psychiatric complications should be anticipated in patients undergoing resection of a large skull base tumor affecting the temporal lobe. The exact mechanism in this process is not clear; however, it is important to clinically differentiate treatable etiologies such as steroid-induced psychosis and postoperative delirium.