BACKGROUND: Breast cancer (BC) constitutes a significant public health challenge in Italy, with a considerable impact on healthcare resources and societal costs. Despite advancements in diagnostics and therapies, the economic burden of BC remains substantial, necessitating a comprehensive evaluation to inform healthcare policy and resource allocation. The aim of this study is to estimate both direct health costs and social security costs related to BC. METHODS: This study utilized real-world data from the Italian Health Information System (HIS) and Local Health Unit (LHU) Umbria 2 HIS databases spanning 2010-2019. Direct health costs, encompassing hospitalizations, outpatient visits, and drug prescriptions, were assessed alongside social security costs associated with BC-related work inability. Statistical analyses and probabilistic models were employed to estimate costs and evaluate trends over time. RESULTS: The analysis revealed an annual cost of €273 million for hospital admissions related to BC in Italy, with metastatic BC (MBC) incurring the highest average annual cost per patient (€5018). When outpatient visits and drug consumption were incorporated, the mean annual cost per patient in LHU Umbria 2 rose to €11,380 for MBC. Social security costs, predominantly comprising disability benefits (DBs), totaled €579 million annually. Overall, the study estimated the total annual economic impact of BC in Italy to exceed €1 billion, with social costs representing 50.4% of the total burden. CONCLUSIONS: This comprehensive assessment underscores the substantial economic strain imposed by BC in Italy and highlights the need for early detection and intervention strategies to mitigate costs and enhance patient outcomes. These findings offer valuable insights into the economic landscape of BC, guiding policy decisions and resource allocation efforts aimed at optimizing BC management and alleviating its societal burden.