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Renal cell carcinoma (RCC) accounts for about 90% of all tumors arising from the kidney. It is the most fatal and aggressive of all urologic neoplasms. About 25 and 40% of patients present with metastasis and recurrence, respectively, after surgery for clinically localized tumors. Discovering superior prognostic markers is still a chief target so as to improve the choice of the patient for particular therapeutic approaches.This study included 44 cases of RCC classified as follows: 30 cases of clear cell RCC, nine papillary RCC, and five chromophobe RCC. All patients underwent radical nephrectomy with no history of radiotherapy or chemotherapy. Immunohistochemical staining of all cases using P21 and peroxisome proliferator-activated receptor gamma (PPARγ) was done.The immunohistochemical expression of p21 was positive in the nuclei of 29 out of 44 (66%) RCC cases. PPARγ expression was positive in 34 (77%) out of 44 cases. P21 expression was significantly correlated with larger tumors (P=0.01), higher Fuhrman’s grade (P=0.01), higher tumor stage (P=0.02), and vascular invasion (P=0.04). PPARγ expression, as well, was significantly correlated with larger tumors (P=0.017), higher stages (P=0.001), and vascular invasion (P=0.012). The relation between the expression of p21 and PPARγ and patient’s outcome was statistically significant (P=0.05 and 0.04, respectively) with better overall survival for patients with negative p21 and PPARγ expression.P21 and PPARγ are strongly associated with the prognosis of RCC and their immunohistochemical expression may help in recognizing the suitable patients for therapy.