Background: Although Polycystic Ovary syndrome (PCOS) is a common endocrine disorder among women of reproductive age; is unclear whether PCOS increases the risk of subsequent development of, Gynecologic cancers namely breast cancer. The present study we aimed to compare the antitumoral ability of peripheral blood mononuclear cells (PBMCs) of women with PCOS with that of healthy controls using the co-culture system between effector cells and target tumor cell lines. Materials & Methods: PBMCs were isolated from 25 women with PCOS and 25 non hirsute eumenorrheic healthy controls by density gradient centrifugation ficoll. Breast tumor cell lines (MDA-468, MCF-7) were incubated as the two target cells and were cultured adjacent to PBMCs in the transwell co-culture system. Proliferation rate of the effectors cells evaluated by BrdU cell proliferation assay after 48 and 72 hours and T CD3+ lymphocytes were assessed using flow cytometry. TNF-α cytokine production was evaluated in cell culture supernatant by sandwich ELISA technique. Results: After 48 hours incubation with MDA-468 and MCF-7, the mean proliferation score of PBMCs was significantly higher in women with PCOS compared to that of healthy controls (921.04; P=0.021 vs 287.6; P=0.002, respectively). In PCOS women, after 72 hours of incubation, TNF-α concentration was significantly reduced compared to 48-hour cultures (921.04 ± 271.4 pg/dl vs 545.6 ± 151.1 pg/dl at 48 h and 72 h intervals respectively, P<0.05); it was increased in healthy controls. There was no significant difference in CD3+ CD8+ cells between the PCOS group and healthy controls. Conclusion: The ability of PBMCs to produce of TNF-α in women with PCOS decreased gradually; as a result of which they may lack the ability required to form an in vitro efficient antitumor response to breast tumor cell lines. It is assumed that threshold activation of mononuclear cells is reduced in women with PCOS and a low-grade inflammatory condition may provide a positive background for arising myeloid derived suppressor cells (MDSCs).