Renal cell carcinoma (RCC) is a common malignancy of the kidney and accurate prediction of prognosis is valuable for the design of adjuvant therapy and counseling and effective scheduling of follow-up visits. Molecular genetic investigations of CD44 and P53 in RCC may be helpful in this regard. We studied the CD44 and P53 expressions semi-quantitatively on paraffin-embedded specimens of 64 RCC patients (37 male/27 female) who underwent surgery from 2003 to 2008 by immunohistochemistry and analyzed the correlation of P53 and CD44 expression in RCC and outcome. Thirteen of 64 (20.3%) specimens were P53 positive, 30/64 (46.9%) were CD44 positive and five tumors with positive P53 expressed CD44 protein (P = 0.5). A statistically significant correlation was not found between CD44 and P53 expression (P = 0.5) and age (P = 0.07), sex (P= 0.3), tumor size (P = 0.7), grade (P = 0.23), vascular invasion (P = 1.00) and ureteral invasion (P = 1.00). Furthermore, a significant correlation was not found between P53 expression with age (P = 0.3), sex (P = 0.7), tumor size (P = 0.7), grade (P = 0.1), vascular invasion (P = 1.00) and ureteral invasion (P = 1.00). According to our findings, only P53 expression is generally accompanied by non-conventional subtype tumor.