Background: Despite advanced therapy of renal cell carcinoma (RCC), up to 40% RCC develop recurrence with high metastatic rate and continues to be one of the fatal forms of cancer. Therefore, detecting new biomolecular markers for prognosis of RCC is important and a major need. Relevant markers of CSCs and angiogenic may serve as prognostic biomarkers of RCC. However, their actual prognostic significance remains inconclusive. Aim of the work: we planned this study to evaluate CD133 and VEGF immunohistochemical expression in renal cell carcinoma cases and its correlation with clinicopathologic data to evaluate their clinical significance and prognostic value. Methods: this study was carried out on 50 cases of radical nephrectomy specimens. Hematoxylin and eosin-stained sections from all cases were re-evaluated and further stained immunohistochemically stained sections were done by using antibodies against CD133 and VEGF. Results: expression of CD133 was down -regulated with the level of malignancy of the RCC and was tightly correlated with tumor grade (p=<0.001), capsular invasion (p=<0.001) and grade of lymphocytic infiltrate (p=<0.001), while, there were no significant associations between CD133 expression and tumor stage, the type, size, TNM stage grouping and tumor laterality. Expression of VEGF was associated with high grade (p<0.001) and clinical stage (p=0.026), large size (p=0.008), capsular invasion (p=<0.001), nodal invasion (p=0.011) and grade of lymphocytic infiltrate (p=0.002) of RCC. There was a statistically significant correlation between CD133 and VEGF with adverse relation between the two markers. Conclusions: our study demonstrated that the expression of CD133 was down -regulated with the level of malignancy of the RCC and was tightly correlated with tumor grade, capsular invasion and grade of lymphocytic infiltrate. These facts demonstrated that CD133 play an important role in the development and progression of RCC. Elevated expression of VEGF is a characteristic feature of high grade and stage, large size and capsular invasion of RCC. There was a statistically significant correlation between CD133 and VEGF with adverse relation between the two markers.