Overexpression of the ERBB-2 protein has become a target of the anti-neoplastic treatment in patients with invasive duct carcinomas of the breast with a monoclonal antibody trastuzumab (Herceptin, Genentech). From this reason the immunohistochemical (IHC) evaluation of ERBB-2 protein expression is crucial. However, there are patients in whom the IHC investigation is biased by a subjective evaluation among cases considered negative (in the range of 1+) and positive (2+), and among cases considered positive 2+ and 3+. In such cases it is advisable to complement the IHC investigation by detection of copy numbers of the ERBB2 gene with fluorescence in situ hybridization (FISH). The overexpression of the protein is caused by the gene amplification in a majority of cases. The patients, whose carcinomas show overexpression of the ERBB-2 protein and the overexpression is caused by a significant gene amplification, profit from the Herceptin therapy. In this review we focus also on the methodology of FISH in paraffin sections and tissue imprints with respect to the detection of copy numbers of chromosome 17 and the ERBB2 gene.