The objective of the present study was to determine whether progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) status differs by menopausal status in estrogen receptor (ER)-positive breast cancers. We retrospectively analyzed the clinicopathological data of 588 with operable ER(+) breast cancers patients. ER, HER2 and PgR expression in the tumor specimens were examined by immunohistochemistry. The relationship between different variables was assessed by Pearson's χ(2) and Fisher's exact probability tests in univariate analyses. Logistic regression was used for multivariate analyses of relationship between HER2 expression and selected clinicopathological characteristics. Maximum likelihood estimates of the odds ratio (OR) were obtained and 95% confidence intervals (CI) were calculated. In the postmenopausal women with ER(+) tumors, HER2 was independently inversely associated with PgR expression (P = 0.017; OR 3.02; 95% CI 1.22-7.49). An ER(+)/PgR(-) tumor was 3.02 times more likely to express HER2 than an ER(+)/PgR(+) tumor in the postmenopausal women. However, an ER(+) tumor in the premenopausal patients failed to show an independent relationship between HER2 and PgR. Menopausal status played a very important role in determining HER2 and PgR status in ER(+) breast cancer patients. HER2 was independently inversely associated with PgR only in the postmenopausal women with ER(+) breast cancers but not in the premenopausal ones. Copyright © 2011 Elsevier Ltd. All rights reserved.