Ovarian cancer is influenced by exogenous and endogenous estrogens as suggested by experimental and epidemiological evidence. Estrogen receptor beta is a predominant estrogen receptor in the normal ovary. Polymorphisms in the estrogen receptor beta gene (ESR2) might influence epithelial ovarian risk through regulation of cell proliferation and apoptosis. This population-based case-control study included 313 women with epithelial ovarian carcinoma and 574 controls, frequency-matched on age and ethnicity. Unconditional logistic regression was used to test associations of rs1271572, rs1256030, rs1256031, and rs3020450 ESR2 genotypes with ovarian cancer risk. Compared to homozygous common allele carriers, homozygous carriers of variant alleles for rs1271572 [odds ratio (OR) = 1.79, 95% confidence interval (CI):1.15-2.79, p global = 0.01] and rs1256030 [OR = 1.67, CI: 1.08-2.59, p global = 0.04], and women with haplotypes, including variant alleles of rs1271572, rs1256030, and rs1256031 SNPs [OR = 1.75, CI: 1.17-2.63, p global = 0.007], had significantly increased risk of ovarian carcinoma. The association of the rs1271572 genotype was strongest among women who had never used contraceptive steroids (p for interaction = 0.04). Our data suggest that ESR2 might be a susceptibility marker for epithelial ovarian cancer.