Breast cancer presents as a heterogeneous disease, not only for the clinic and histology, but also in genetic expression profile. Studies using cDNA microarrays have recently led to the re-classification of invasive breast carcinomas, based on their molecular signature, into three main groups: luminal; HER2 (Human Epidermal Receptor 2) overexpressing, and basal-like. Although the latter group is the least prevalent it is the most aggressive one, lacking a target based therapy, since their main characteristic is being negative for hormonal receptors or HER2. So, it is of paramount importance to try to unravel their histogenic origin and characterize their molecular and immunohistochemical profiles. EGFR (Epidermal Growth Factor Receptor), which is overexpressed in a high proportion of these carcinomas, is a potential therapeutic target, and clinical trials with inhibitors of its activity may represent important advances in basal-like breast carcinomas therapy.