In breast cancer patients, the expression of steroid hormone receptors (HR:ERalpha/PR) appears inversely correlated with Her2/neu (not all reports agree on this negative correlation). Moreover, some but not all studies suggest that HR+/Her2/neu+ patients have a poor response to endocrine therapy, making this special group a matter of debate. In this prospective study we have analyzed the clinical outcome of our HR+/Her2/neu+ patients (n=51) selected from 516 consecutive stages I-II cases, with a follow-up 5-10 years (mean 7.3), treated with standard adjuvant therapy with tamoxifen (TAM) (TAM alone or TAM after chemotherapy). This group was compared with the HR+/Her-2/neu- patients (n=129) treated also with TAM. The tumor biopsies were studied by immunohistochemistry. We found that the association HR+/Her2/neu- was 2.5 times higher than the association HR+/Her2/neu+ (25% versus 9.9%, respectively). Our study also showed that the disease free survival (DFS) of the patients co-expressing HR and Her2/neu was significantly lower than those expressing HR but lacking of Her2/neu (p<0.001). A similar result was obtained when the overall survival (OS) was evaluated (p=0.001). All of these patients received hormone therapy with TAM, alone or after chemotherapy. When the analysis was performed in the patients treated with TAM alone, again the expression of Her-2/neu had a negative impact on both the DFS and the OS (p<0.05).