Estrogen receptor alpha 36 (ERα36), a truncated variant of ERα, is located in cytoplasm and membrane that is different from other nuclear receptors of ERα family. ERα36 is involved in progression and treatment resistance of a variety of carcinomas. However, the clinical and prognostic significance of ERα36 in renal tumors have not been fully elucidated.Here, renal tumor tissues from 125 patients were collected and immunohistochemical stained with ERα36 antibody. ERα36 expression level and location in these cases were analyzed for their correlations with clinical characteristics. The differential diagnosis value was also assessed for benign and malignant renal tumors, as well as its prognostic value.The results showed that membrane ERα36 expression was rarely detected in benign tumors but predominantly observed in malignant renal tumors. Kaplan-Meier analysis indicated that significant correlations of high ERα36 level and ERα36 membrane expression were correlated with both poor disease-free survival and overall survival. Univariate and multivariate analysis confirmed that both ERα36 high expression and membrane location can serve as unfavorable prognostic indicators for renal cell carcinoma.It is thus concluded that membrane ERα36 expression is valuable for differential diagnosis of malignant renal tumors from benign ones. Both ERα36 high expression and membrane location indicate poor prognosis in renal cell carcinoma.