Objectives: The purpose of this study was to evaluate the correlation between the levels of cyclooxygenase- 2 (COX-2) expression with clinicopathologic features and determine the impact on prognosis in patients with renal cell carcinoma (RCC). Methods: Expression of COX-2 was evaluated immunohistochemically in RCC tissues from 62 patients who underwent radical nephrectomy between 1996 and 2004. Percentage of COX-2 staining was scored as 0 (negative), 1 (1-24%), 2 (25-49%), 3 (50-74%), and 4 (75-100%). Immunohistochemical COX-2 staining score (ISS) was defined as summation of intensity and percentage of COX-2 staining. Results: Twenty-seven patients (43.5%) with a median follow-up of 47.8 (25-115) months stained positively for COX-2. COX-2 expression was positive in 37.1%, 50%, and 66.7% of patients with stages 1, 2, and 3, respectively (P = 0.46). Correlation between ISS and pathological stage was statistically significant (P = 0.005). Multivariate regression analysis revealed no clinicopathologic parameter as independent predictors of progression. Kaplan-Meier analysis revealed statistically significant different survival rates in tumor stage, grade, and ISS. Conclusion: Although COX-2 expression is not an independent predictor of progression in patients with RCC, patients with higher ISS values have significantly shorter progression-free survival rates. These results might be important to the clinician because positive COX-2 expression of a certain RCC might necessitate early adjuvant systemic therapy to delay the progression of RCC. For this reason, there is a need for innovative, prospective, and randomized studies in patients with positive COX-2 expression that will display the impact of systemic therapies in these patients. © Springer Science+Business Media B.V. 2008.