Background: The epidermal growth factor receptor HER2 is overexpressed or amplified in 25%–30% of patients with breast cancer. The mechanism behind HER2 amplification is unknown, but may be a patho-physiological phenomenon caused by continuous stimulation and activation of the HER1-4 system. We have mapped the protein concentrations of HER1-4 in breast cancer tissue, autologous reference tissue, normal breast tissue and serum samples, to see whether non-cancer cells from these patients express a protein profile indicating general activation. Methods: Tissue samples from malignant and adjacent normal breast tissue (autologous reference tissue) were collected from 118 women consecutively admitted for surgical treatment of breast cancer. In addition, 26 samples of normal breast tissue were collected from healthy women having breast reduction surgery. The tissue samples were homogenized and the proteins extracted. The tissue and serum concentrations of HER1-4 were determined quantitatively using a commercially available enzyme linked immunosorbent assay (ELISA) method. Results: HER1 was down regulated in cancer tissue when compared to autologous reference tissue (p=8×10−6), while HER2 (p