Objectives: To differentiate between renal cell carcinoma (RCC) subtypes through the expression of different microRNAs and immunohistochemical markers and its correlation to the disease outcomes. Methods: We examined the stored fresh frozen specimen of 137 RCC and adjacent healthy renal tissue for the quantitative RT-PCR expression of five microRNAs (miRNA222, miRNA221, miRNA126, miRNA200b, miRNA200c) and the immunohistochemical staining severity of AMACR, CK7, CD10 and CD11. The relative expression of the markers were compared between different RCC subtypes and correlated to the disease stage, grade and recurrence. Results: Clear RCC (cRCC) can be differentiated from other subtypes by the higher expression of miRNA126 (P<0.001, ≥ 7.5 has 98% sensitivity and 95% specificity) and staining for CD10 (P<0.001). However, miRNA126 did not correlate with the stage (r2=0.1, p= 0.2), grade (r2=0.04, p=0.07), L.N stage (r2=0.05, P=0.6) or disease recurrence (r2=0.06, p=0.5). Papillary RCC (pRCC) can be differentiated from chRCC and oncocytoma by higher expression of miRNA 221 and higher staining for AMCAR and CD10 and less staining for CD117 (p<0.001). Chromophobe RCC (chRCC) showed significantly higher expression of miRNA 200c. MiRNA 200c expression ≥ 0.43 has 70% sensitivity and 70% specificity for detection of chRCC (AUC=0.7 and P= 0.001). Conclusion: Different microRNAs together with the immunohistochemical markers seem to be a useful clinical tool to differentiate RCC subtypes. Further studies are required to study its implication on the disease management outcome and response to new targeted therapy.