HER-2 and potentially topoisomerase II alpha are clinically useful parameters in breast cancer. The gene status and protein expression are, for both markers, used as predictive markers in research or clinical practice. New guidelines for HER-2 testing from ASCO and CAP have been recently published and new definition for HER-2 gene amplification will probably decrease the impact of polysomy 17 on HER-2 FISH status evaluation. Different forms of HER-2 receptor (p95HER-2, p185HER-2) could be considered as prognostic or predictive markers in the future if preliminary results are confirmed. The topoisomerase II alpha case is more complex as the results of preclinical and clinical studies seem to be contradictory. The results of the clinical studies are so far, encouraging but need to be confirmed. Moreover studies should be designed to define which one of the protein or the gene or both should be evaluate as predictive markers of response to anthracyclines chemotherapy. More studies are needed today to consider this marker for daily practice.