In this study, we aimed to examine the relationship between atypical depression and insulin resistance (IR) in patients with polycystic ovary syndrome (PCOS) and major depression. A total of 176 subjects (69 patients with PCOS, 58 patients with depression, and 49 healthy controls) were included in the study. The Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAT), the Beck Hopelessness Scale (BHS), and the Scale for Suicide Ideation (SSI) were administered. Data concerning their height, weight, fasting a.m. serum levels of insulin, glucose level, and total testosterone level were collected from all participants. The body mass index (BMI) and the Homeostasis Model Assessment Insulin Resistance index (HOMA-IR) were both calculated. 34 (49.3%) of the PCOS patients met the criteria for depression. 26 (76.5%) of them had atypical depression, 8 (23.5%) had non-atypical depression. 27 (46.6%) of the 58 depressed patients had atypical depression. Insulin resistance was higher in the PCOS patients than in the control subjects and the depression patients. There was no association between atypical depression and IR in patients with PCOS and depression. We concluded that there is no relationship between IR and atypical depression.