The aim of th present study was to evaluate the effectiveness of fluorescence in situ hybridisation (FISH) , as a screening test, in moderately- (G2) or poorly - (G3) differentiated breast cancers of the ductal (IDC) and lobular (ILC) histotypes and distant metastases. HER2 FISH was performed on 486 G2 and 477 G3 both of IDC and ILC histotypes and in 241 metastases. A significant difference in the HER2 amplificaion was observed between G2 (14,8) and G3 (31.9%), with no difference according to the histotype. However, the rate of amplificaion increased to 36% in the G2/hormone receptor negative cases as compared to 10,6% in the G2/receptor-positive cases (p<0.0001). HER2 was amplified in 17% of metastases with some differences depending on the location. These data suggest that the HER2 FISH analysis may be an effective screening test in breast cancer metastases and G3 tumors, irrespective of the hormone receptor status or presence of lymphovascular invasion.