The actual predictive value of oestrogen receptor (ER) beta for treatment decisions in breast cancer is still unclear. Retrospective studies using preoperative systemic therapy (PST) revealed that chemotherapy but also endocrine therapy can lead to alterations in expression levels of ERalpha and progesterone receptor (PR). The main purpose of this study was to compare ERbeta expression levels before and after neoadjuvant chemotherapy or endocrine therapy and to explore a possible predictive value of ERbeta. Matching 'baseline' biopsies and post-therapy surgical specimens of 69 breast cancer patients treated with neoadjuvant anthracycline- or taxane-based chemotherapy or with aromatase inhibitors were analyzed for expression levels of ERalpha, PR, total ERbeta (ERbetat), ERbeta1, ERbeta2 and the proliferation-related antigen Ki-67 using immunohistochemistry. A marked expression of ERbetat significantly correlates with low proliferation rates after PST (p=0.0013) and with response to it. Further most tumours decreased ERbeta1 expression with PST. A marked ERbeta2 expression was observed predominantly in responders and significantly decreased during chemotherapy (p=0.047). Results on ERalpha and PR corroborate findings of previous studies. Our data demonstrate that changes of ERbeta expression occur during PST and that total ERbeta expression and ERbeta2 may have a predictive value for PST.