This study aims to (1) evaluate the immunohistochemical expression of ERα, ERα36 and ERβ in combination in human renal cell carcinoma (RCC) and nearby non-tumorous tissue (2) correlate their expression pattern with the clinicopathological parameters and prognosis of the patients; this may provide a new insight into prediction of the disease outcome and understanding its progression. The three markers showed positive cytoplasmic (± membranous) staining pattern in tumor cells. The tubules in the nearby non-tumorous tissue showed either nuclear (± cytoplasmic) staining pattern (ERα and ERβ) or only cytoplasmic staining pattern (ERα36). The mean of cytoplasmic expression of ERα, ERα36 and ERβ was significantly higher in association with poor prognostic factors: larger tumor size (P<0.0001) for each, late clinical stage (P<0.0001) for each, higher nuclear grade (P = 0.003, P = 0.002 and P = 0.022) respectively, and presence of lymphovascular invasion (P<0.0001, P = 0.006 and P<0.0001) respectively. We have demonstrated for the first time that patients whose tumors express high cytoplasmic levels of ERα, ERα36 or ERβ experience shorter overall survival and disease-free survival. The independent role of ER subunits as markers of poor prognosis is proven only for ERβ and ERα36 but not ERα. In conclusion, our results indicate that the main staining pattern of ERα, ERα36 and ERβ in RCC is cytoplasmic with relation of this pattern to bad prognosis. So we can suggest the assessment of these receptors as markers of poor prognosis in RCC patients.