EGFR and HER2 are highly expressed in 15-30% of breast cancer tissues. Therefore, EGFR and its downstream signaling pathways are promising anti-tumour targets. HER2 overexpression is often associated with estrogen receptor (ER) and progesterone receptor (PR) negativity, high histological grade, high rates of cell proliferation and lymph node involvement. Moreover, it is correlated with disease aggressiveness, increased rates of recurrence and poorer survival in node-positive breast cancer patients, whereas the prognostic significance in patients with node-negative tumors remains somewhat controversial. This paper focuses on the therapeutic strategy for treatment of HER2 overexpressing breast cancer in advanced stages of disease, as well as in the adjuvant and neo-adjuvant settings.