c-erbB2 is a proto-oncogene that encodes the trans-membrane protein p185. This protein shares considerable sequence and structure homology with members of the epidermal growth factor receptor family and it is believed to cooperate with these receptors in the signal transduction process in order to control cell proliferation. Overexpression of c-erbB2, with or without gene amplification, is frequently found in breast cancer, and a body of evidence suggests it is implicated in the development of resistance to the antiestrogen tamoxifen. Scientific evidence strongly supports a correlation between c-erbB2 overexpression and lack of efficacy of tamoxifen in both advanced and adjuvant settings. However, given the important therapeutic repercussion of this topic, further studies are required before c-erbB2 evaluation can be routinely used to select patients who are likely to benefit from tamoxifen administration.