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Peroxisome proliferator-activated receptor γ (PPARγ) belongs to the nuclear receptor superfamily of PPARs (PPARα, PPARβ/δ, PPARγ). Numerous studies have concentrated on the key role of PPARs in inflammation and a variety of cancers which include prostate, breast, glioblastoma, neuroblastoma, pancreatic, hepatic, leukemia, and bladder and thyroid tumors. This review, specifically deals with anti-tumor and tumorigenicity effects of PPARγ and its natural and synthetic agonists including Troglitazone, Cladosporol A, B, 15-Deoxi-Δ-Prostaglondin J2 (15-d-PGJ2), Ciglitazon, docosahexaenoic acid, eicosapentaenoic acid Alpha-eleostreac acid, Amorfrutin C, Sphingosine 1-phosphate, Evodiamine, Excavatolide B vs respected antagonists as GW9662, bisphenol-A-diglycidyl-ether. Considering the contradictory role of PPARγ on tumorigenicity, a number of studies demonstrate mechanisms involved in tumorigenicity effects of PPARγ agonists while several studies suggest key roles of PPARγ agonists in anti-proliferation, metastasis, angiogenesis, apoptosis and immunomodulatory through activation of signaling pathways in different cancer cells as well as in cancer stem cells. The aim of this review is summarizing of tumorigenicity and anti-tumorigenicity activities of PPARγ agonists and antagonists as well as therapeutic activities of these reagents as a coadjutant drug in the treatment of different cancers.