Background: Cancer stem cells (CSCs) represent a population with tumour initiating, self-renewal, and differentiation potential. The aim of the work is to evaluate the expression patterns and clinical significance of chemokine receptor type 4 (CXCR4) as a novel CSC marker in renal cell carcinoma (RCC). Material and Methods: the expression of CXCR4 was examined in 50 well-defined renal tumour tissues, including 28 clear cell renal cell carcinomas (ccRCCs), 11 papillary renal cell carcinomas (pRCCs), and 11 chromophobe renal cell carcinomas (ChRCCs) with immunohistochemistry staining, the association between expression of this marker and clinicopathologic parameters, was then analyzed.  Results: CXCR4 expression & intensity was significantly correlated with RCC clinicopathological features as grade, stage, size of the tumor and microvascular invasion (MVI) but there was insignificant correlation between histopathological types and the pattern of CXCR4 expression and its intensity . Conclusion: increased CXCR4 expression was associated with more aggressive tumour behaviour in RCC patients, especially in pRCC and ccRCC subtypes due to their more metastatic behaviour. These findings suggest that CXCR4 can be considered as a novel prognostic and therapeutic marker for targeted therapy of renal carcinoma.