Objective: Arachnoid cysts are the most common intracranial cysts and their role in causing psychiatric symptoms is often underrecognized. This report is a case of a patient with intracranial arachnoid cyst and clinical finding of depression. Case report: A 53-year-old woman patient presented with unspecified depressive symptoms and the brain MRI finding showed an arachnoid cyst about 3cm in size over the right temporal pole. She showed dramatic clinical response to duloxetine but the discrepancy between her verbal IQ and performance IQ were still persisted. Conclusion: This case report is the first to show an association between arachnoid cysts and clinical depression, and to highlight the use of an unusual approach in dealing with a patient with brain lesions and psychiatric symptoms.