Abstract Background: Renal oncocytoma, chromophobe RCC, and conventional RCC (granular cell type) have different prognosis. The differentiation between them sometimes is difficult and may cause a diagnostic dilemma. Aim of Study: To reveal the better immunohistochemical diagnostic markers for differentiation between Chromophobe Renal Cell Carcinoma (ChRCC), Clear Cell Renal Cell Car-cinoma (CCRCC), and oncocytoma. Material and Methods: We reviewed one hundred and fifty cases of renal cell carcinoma: ChRCC (100 case), CCRCC (25 cases) and RO (25 cases). We carried out comprehensive immunohistochemical profiling using Hales Colloidal Iron stain (HCI), and 6 markers: Vimentin, CK7, CD 10, CD 117. EpCAM, and S100. Results: Our results demonstrated a statistically significant difference in the expression of Hales colloidal iron among the studied renal tumors (p-value <0.0001) as 94% of cases of chromophobe renal cells carcinoma showed positive staining for Hales colloidal iron, but cases of clear cell renal cell carcinoma and oncocytoma showed no staining for Hales colloidal iron stain. All cases of ChRCC were negative for vimentin. 72% of CCRCC and 8% of oncocytoma showed cytoplasmic positivity for vimentin. This difference in the expression was statistically significant (p-value <0.0001). 76% of ChRCC cases showed cytoplasmic immunoreactivity to CK7, while 8% of CCRCC and 4% of oncocytoma showed such cytoplasmic immunoreactivity for CK7. These results were statistically significant with p-value <0.0001. We found that CD 10 showed statistically significant correlation with tumour type with p-value 0.025. CD 117, EpCAM, S100A1 showed statistically significant correlation with tumor type with p-value <0.0001. Conclusion: We concluded that the best panel of markers that can differentiate between the three studied renal tumour types by calculating sensitivity and specificity of each marker in each tumour type we found that the best panel is Vimentin, EpCAM and S100A1.