Aim: To investigate co-expression of ATRX and HIF-1α in kidney neoplasm in relation to its origin. Introduction: A heterogenous group of kidney tumors is believed to arise from a variety of specialized cells along the nephron – proximal tubules [Clear cell Renal Cell carcinoma (ccRCC) and papillary RCC (pRCC)] and collecting tubules [chromophobe RCC (chRCC) and oncocytoma]. ATP-dependent helicase (ATRX) is a chromatin remodeling protein involved in gene regulation and aberrant DNA methylation during cancerogenesis. Activation of hypoxia inducible factor (HIF-1α) is an early event in most RCC following inactivation of the VHL tumor suppressor gene. Material and Methods: A total of 46 kidney tumors (n=33 ccRCC, n=1 mRCC, n=4 pRCC, n=5 chRCC and n=3 oncocytomas) was immunohistochemically analyzed for ATRX and HIF-1α expression. Results: Diffuse and focal positivity of ATRX expression was found in 51.5% of ccRCC, while 54.5% had HIF-1α positivity. Co-expression of ATRX/HIF-1α was not related to nuclear grade and stage of ccRCC. Metastatic ccRCC had strong expression of both markers. pRCC type II showed weak ATRX/HIF-1α expression, while pRCC type I was negative for both markers. Interestingly, all analyzed oncocytomas and chromophobe RCC were negative for ATRX/HIF-1α. Conclusion: Our results suggest that signaling pathways have different patterns of activation/suppression of ATRX/HIF-1α in oncocytomas and chRCC compared to other RCC types. Downregulation or loss of ATRX/HIF-1α coexpression in benign tumors should be further investigated in order to determinate mechanisms of ATRX/ HIF-1α signaling transport renal neoplasm with different origin.