•Breast cancer is a major cause of morbidity, disability and mortality among women.•Epidemiological trends describe global disparities in breast cancer-related mortality.•Disparities in breast cancer result from variable access to early detection, treatment and palliative care.•Investing in breast cancer control generate broad population impact, particularly in countries with high/increasing burden.•WHO-led Global Breast Cancer Initiative (GCBI) is a programmatic platform to tackle global disparities in cancer care.•GBCI aims to improve the capacity for breast cancer care to result in population health and broader socio-economic impact. Breast cancer is the leading cause of cancer morbidity, disability and mortality in women, worldwide. Overall, in 2020, it was the most diagnosed malignancy. Differences in breast cancer mortality have been historically evidenced, as a result of disparities in access to diagnosis, treatment and palliative care. Epidemiologic trends in the last decades display three main patterns of breast cancer mortality: some high-income countries report continuous substantial improvements exceeding 2% annual mortality reduction; however, many low- and middle-income countries (LMICs) have stagnant or even increasing mortality rates. Population-based studies show that investing in breast cancer control, based on a primary health care approach, and expanding the cancer treatment capacity can portend population health benefits, with positive changes of the epidemiological adverse trajectories. Framed as part of the political commitment to the Sustainable Development Goals Agenda, World Health Organization (WHO) has recently launched a global initiative to tackle disparities in breast cancer mortality. The WHO-led Global Breast Cancer Initiative (GBCI) is framed across 3 pillars, to address key determinants of the cancer-related outcomes: health promotion and early detection, timely access to diagnosis and treatment, comprehensive breast cancer treatment, palliative and survivorship care. GBCI is a systematized approach, with the goal to (i) increase the fraction of newly diagnosed invasive cancers being stage 1 or 2 at diagnosis (60% or more), (ii) ensure diagnostic work-up to be completed within 60 days from the first connection with the primary healthcare providers to avoid delays in diagnosis and treatment and (iii) assure 80% or more women with breast cancer to undergo and complete multimodal treatments. GBCI will pursue a comprehensive and multisectoral approach, to deliver population health, social and economic benefits, ultimately intended as an entry point for health system strengthening and for the broader cancer control.