Our objective is to investigate the possible induction of manic symptoms by quetiapine through a case report with recurrent major depression. A 44-year-old female with a DSM-IV diagnosis of major depressive disorder was hospitalized for a recent set of depressive symptoms, including anxiety, sleep disturbance, lack of energy, and unhappiness. During a 15 years history of depressive disorder, she had experienced residual MDD symptoms despite being on multiple antidepressant medication. The patient had no history of substance abuse or manic or hypomanic episodes. Her family also had no history of manic or hypomanic episodes. Before recent hospitalization, Ms. A’s psychotropic medications, which had been started by her psychiatrist 10 weeks ago, were paroxetine 40 mg/day combined with mirtazapine 30 mg/day. First of all, mirtazapine and paroxetine were discontinued, and treatment with escitalopram 10 mg/d and amitriptyline 25 mg/day were started. Over the course of 10 days, amitriptyline dose was increased to 50 mg/day. During this time, the patient’s depressive symptoms did not improve; instead, she complained sedation as well as dry mouth and constipation, which are known to be the common adverse effects of amitriptyline and than this medication was discontinued. Quetiapine was then gradually titrated up to 300 mg/day for a period of 5 days. One week later, the patient showed a remarkable improvement in her depressive and anxiety symptoms as well as sleep disturbance. She developed mania two weeks after the initiation of 300 mg/d of quetiapine. The manic symptoms were thought to be related with quetiapine and this therapy was stopped. Manic symptoms improved dramatically after discontinuation of quetiapine. The 5-HT2 antagonistic action of quetiapine may disinhibit the dopaminergic system enhancing dopaminergic activity in the forebrain and inşuencing the mood state. It has been reviewed that concerning the induction of hypomania or mania by quetiapine have retrieved the presence of seven similar case reports or series. However; its manic/hypomanic induction properties should not prevent its administration to patients suffering from major depression.