Breast cancer is a polymorphic disease and, until now, nodal invasion and steroid receptor levels remain the most powerful and widely used prognostic indicators. Molecular oncology has proven the importance of somatic genetic events in cancer genesis and evolution. In breast cancer a number of genetic aberrations have been proposed to bear impact on disease outcome. Greatest significance has been associated to ERBB2 amplification and overexpression. More recently p53 mutations have been suggested to bear meaning in terms of cancer evolution. We discuss here the molecular epidemiology of p53 mutations in human breast tumors and the clinico-pathological significance that can be associated to them.