Estrogen receptor alpha (ER alpha) is a well-established prognostic marker in breast cancer. The role of estrogen receptor beta (ER beta) in breast cancers is still under investigation. We aimed to investigate the clinicopathological significance and immunohistochemical expression patterns of ER alpha, total ER beta (ER beta) and its spliced variant ER beta cx in normal breast, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). Our study population comprised 10 normal breasts, 26 DCISs and 44 IDCs. Immunohistochemical expression of these markers was investigated in sections of formalin-fixed, paraffin-embedded blocks by 2 observers. In invasive ductal carcinomas, ER beta expression had a significant positive correlation with ER alpha expression (p = 0.013), while ER beta cx expression was significantly associated with the presence of lymphovascular invasion (p = 0.046). There was a significant relationship between ER alpha expression and low histological grade (p < 0.0001). Similarly, ER alpha+/ER beta+ tumors (p = 0.004) and ER alpha+/ER beta cx+ tumors (p = 0.008) were significantly associated with low histological grade, too. ER alpha expression (p = 0.009), ER beta cx expression (p = 0.048) and ER alpha+/ER beta+ coexpression (p = 0.002) increased significantly in progression from normal breast to invasive ductal carcinoma. Expression of ER alpha correlates with less aggressive phenotypic features, and ER beta expression is positively correlated with ER alpha expression in breast cancer. ER beta cx is associated with aggressive features and can take part in the progression of invasive carcinoma. Increase in ER alpha+/ER beta+ coexpression, ER alpha expression and ER beta cx expression in breast cancer progression indicates an enhancement in ER expressions or an alteration in expression patterns of different ER variants during mammary carcinogenesis. (C) 2012 Elsevier GmbH. All rights reserved.