Abstract: The aim of the study was to evaluate the roles of screening activation and hormone replacement therapy discontinuation on the recent declining breast cancer incidence trends in Italy. We analyzed 41,358 invasive female breast cancers incident during 1991–2004 in six Italian population-based cancer registries. Overall and age-specific incidence trends were evaluated using Joinpoint analysis. In addition to calendar years, data were analyzed on a years-since-screening-activation basis. Annual percentage change of standardized rates was computed. There were statistically significant increasing trends for women 40–44 and 45–49 years that did not change after screening activation. On the contrary, for women 50–69 years old and for those 70+ years, the increasing trends flattened around 2 years after screening activation. The prevalence of hormone replacement therapy use in Italy is and was rather low. In conclusion, the recent tendency toward stabilization observed in Italy for female breast cancer incidence rates in women aged 50 years or more follows the introduction of mammographic screening.