Our current findings lend support to forthcoming prospective studies aimed to validate the concept that identification of CK5/6-positive immunophenotypes within HER2+ breast carcinomas may be a rapid and accurate method for identifying intrinsic subgroups of biologically aggressive tumors likely to display resistance to trastuzumab ab initio in women diagnosed with HER2+ cancer. This evidence concerns the gene ERBB2 and breast carcinoma.