The aim of this study was to investigate the relationship of cyclooxygenase (COX)-2 and p53 expression with prognosis in patients with conventional renal cell carcinoma (RCC). Formalin-fixed, paraffin-embedded tissue sections of conventional RCC from 92 patients, who had undergone radical nephrectomy, were examined for COX-2 and p53 expression by immunohistochemistry and compared with clinicopathological variables. The COX-2 expression significantly correlated only with tumor size (p=0.049), whereas the p53 expression profoundly correlated with the TNM stage (p=0.024), M stage (p=0.001), and metastasis (synchronous or metachronous; p=0.004). The COX-2 overexpression did not significantly associate with p53 positivity (p=0.821). The survival rate of patients correlated with the p53 expression (p<0.0001) but not with the COX-2 expression (p=0.7506). Multivariate analyses indicated that tumor size, M stage, and p53 expression were independent prognostic factors for cancer-specific survival. The COX-2 expression was not an independent factor. These results show that the increased expression of p53 was associated with metastasis and a worse prognosis in conventional RCC, which suggests that p53 might have played an important role in the progression of conventional RCC. The increased expression of COX-2 was associated only with tumor size, but may not be an important prognostic factor in conventional RCC. No association was observed between COX-2 overexpression and p53 positivity in conventional RCC.