◥Background: Differential associations between ovarian cancer risk factors and estrogen receptor-a (ERa) ovarian tumor expression have been noted; however, no research has assessed estrogen receptor-b (ERb) expression. Thus, in exploratory analyses, we assessed the association of several factors with ovarian cancer risk by ERb tumor status.Methods: We conducted a nested case-control study within the prospective Nurses' Health Study cohorts (NHS/NHSII), with exposures collected through biennial questionnaires. Paraffinembedded tumor blocks were requested for cases diagnosed from 1976 to 2006 (NHS) and 1989 to 2005 (NHSII) and tissue microarrays were stained for nuclear ERb (ERb-nuc) and cytoplasmic ERb (ERb-cyto), with any staining considered positive (þ). We obtained odds ratios (OR) and 95% confidence intervals (CI) using multivariate polytomous logistic regression.Results: We included 245 cases [43% ERb-cyto (þ) and 71% ERb-nuc (þ)] and 1,050 matched controls. An inverse associa-tion was observed between parity and risk of ERb-nuc (þ) (OR, parous vs. nulliparous: 0.46; 95% CI, 0.26-0.81), but not ERb-nuc (-) tumors (OR, parous vs. nulliparous: 1.51; 95% CI, 0.45-5.04; P heterogeneity ¼ 0.04). Conversely, parity was inversely associated with ERb-cyto (-) tumors (OR, parous vs. nulliparous: 0.42; 95% CI, 0.23-0.78), but was not associated with ERb-cyto (þ) tumors (OR, parous vs. nulliparous: 1.08; 95% CI, 0.45-2.63; P heterogeneity ¼ 0.05). Associations for other exposures, including hormone therapy, did not differ by ERb-nuc or ERbcyto status.Conclusions: Our results suggest that parity may influence ovarian cancer risk, in part, through alterations in ERb localization within tumor cells.Impact: Alterations in ERb expression and localization appear to be important for ovarian cancer etiology. Future research should confirm our results and assess potential biologic mechanisms for the observed associations.