Introduction: HER-2 overexpression, a predictive marker of tumor aggressiveness and responsiveness to therapy,occurs in 20-30% of breast cancer.Although breast cancer is a heterogeneous disease, HER-2 measurement is carried out in primary tumor.This study aims to evaluate HER-2 overexpression in primary and metastases and its effect on treatment decisions and to update our results published in British Journal of Cancer at 2005.Patients/Methods:Biopsies from primary breast cancer and corresponding metastases from 88 patients were studied.HER-2 overexpression was evaluated immunohistochemically in all primary and metastatic sites.Positive overexpression in primary and/or metastases was confirmed by fluorescence in situ hybridization (FISH) or by chromogenic in situ hybridization (CISH).Results: Discordance in HER-2 overexpression between primary and metastic sites was 16% (14 of 88 patients).Concordance was found in 74 (84%) of patients (95% Cl: 77-95).In one patient (1.3%) HER-2 was negative in metastasis but positive in primary.In 13 (14.7%) patients HER-2 was positive in metastases and negative in primary (95% Cl: 3.7-20), and 7 of them responded to trastuzumab.Gene amplification by FISH or CISH was found in all metastases with HER-2 positive (+2 and +3) by imuunohistochemistry.Conclusions: Our data suggest that a possible discordance of HER-2 overexpression between primary and metastases should be considered when making treatment decision in patients with primary HER-2-negative tumors who can benefit of treatment with trastuzumab.