Circulating blood biomarkers promise to become non-invasive real-time surrogates for tumour tissue-based biomarkers. Circulating biomarkers have been investigated as tools for breast cancer diagnosis, the dissection of breast cancer biology and its genetic and clinical heterogeneity, prognostication, prediction and monitoring of therapeutic response and resistance. Circulating tumour cells and cell-free plasma DNA have been analysed in retrospective studies, and the assessment of these biomarkers is being incorporated into clinical trials. As the scope of breast cancer intratumour genetic heterogeneity unravels, the development of robust and standardized methods for the assessment of circulating biomarkers will be essential for the realization of the potentials of personalized medicine. In this Review, we discuss the current status of blood-born biomarkers as surrogates for tissue-based biomarkers, and their burgeoning impact on the management of patients with breast cancer.