In the present study, we found that expression of ERβ, but not ERα, increases with tumor stage and grade, and also observed that modification of ERβ signals using estrogens/anti‐estrogens, shRNA knockdown of ERβ and overexpression of ERβ using ectopic cDNA affects RCC cell proliferation, migration and invasion. The gene discussed is ESR2; the disease is renal cell carcinoma.