Simple SummaryImproving the response of breast cancer patients by designing and applying the most appropriate treatment for each case is a major scientific challenge. Given the role of intracellular calcium in cell proliferation, apoptosis evasion and cell resistance, in this review, we discuss its potential for the development of new pharmacological treatments to treat the disease.AbstractCancer is one of the main health problems worldwide. Only in 2020, this disease caused more than 19 million new cases and almost 10 million deaths, with breast cancer being the most diagnosed worldwide. Today, despite recent advances in breast cancer treatment, a significant percentage of patients will either not respond to therapy or will eventually experience lethal progressive disease. Recent studies highlighted the involvement of calcium in the proliferation or evasion of apoptosis in breast carcinoma cells. In this review, we provide an overview of intracellular calcium signaling and breast cancer biology. We also discuss the existing knowledge on how altered calcium homeostasis is implicated in breast cancer development, highlighting the potential utility of Ca2+as a predictive and prognostic biomarker, as well as its potential for the development of new pharmacological treatments to treat the disease.