Determination of HER-2/neu overexpression/amplification is becoming increasingly important. The aim of this study is to elaborate an algorithm for the diagnosis of Her-2/neu status in breast-infiltrating carcinomas. Three hundred five breast-infiltrating carcinomas were selected to determine HER-2/neu overexpression by immunohistochemistry with two different methods: the monoclonal antibody CB11 and the HercepTest. Fluorescence in situ hybridization (FISH) was performed in a subgroup of those cases. Time-consuming and reagent costs were calculated for each of the procedures. HER-2/neu overexpression was found in 16% and 33% of the tumors with the monoclonal antibody (mAb) CB11 and with the HercepTest, respectively. There were 50 cases with immunohistochemical discordant results; most of them were HercepTest score 2+/mAb CB11 negative (37/50). Of those cases, only 27% presented gene amplification. The algorithm consisted of testing all the specimens with the mAb CB11 for selection of positive cases, negative cases are confirmed with the HercepTest, and FISH is performed only in those cases with immunohistochemical discordant results. The algorithm rate of HER-2/neu positivity in our series was 22%. Time and costs are reduced by 60% and 41%, respectively, compared to FISH. The use of the algorithm is feasible, accurate, and cost-effective in relation to FISH.