Present study depicted the role of polymorphisms in estrogen receptor-alpha gene in association with prostate cancer in north Indian population. The study was performed on 157 cases of prostate cancer, 170 cases of BPH, and 170 healthy Indian males diagnosed with prostate cancer and benign prostatic hyperplasia (BPH) and healthy males as controls. Determination of polymorphism in the ER-alpha gene was done by polymerase chain reaction followed by restriction fragment length polymorphism (RFLP) analysis with PvuII and XbaI enzymes. An association was observed between PvuII polymorphism of ER-alpha gene and that of prostate cancer. However, there was no such association with XbaI polymorphism in ER-alpha gene.