Breast cancer is a highly heterogeneous disease due to its diverse morphological features, the variable clinical outcome and the response to different therapeutic options. It is therefore necessary to devise a clinically meaningful classification of the disease, which has to be scientifically sound, clinically useful and widely reproducible. The established histopathological classification has a limited clinical utility, due to insufficient prognostic and predictive power. More recent classification schemes, based on the immunohistochemical characterization of breast cancer for the assessment of hormone receptor status, HER2 gene over-expression or amplification and the proliferative fraction or on gene expression profiles, correlate much better with the clinical outcome and may be used to inform the choice of the systemic therapy.