Abstract: Breast cancer was the first human cancer wherein a personalized treatment strategy was driven by the molecular characterization of patient-specific tumors. However, determination of molecular and intrinsic subtypes based on immunohistochemistry and genome analysis, respectively, has a few limitations. Therefore, the clinical heterogeneity of breast cancer prognosis and treatment remains to be fully understood. The intratumoral heterogeneity (ITH) theory differs from the molecular subtyping of breast cancer. It acknowledges the existence of multiple subtypes within a single tumor (spatial heterogeneity) and the heterogeneous transformation between different phenotypes at different stages (temporal heterogeneity). ITH is driven by cell-state heterogeneity and clone evolution, and is affected by the surrounding microenvironment and metabolic reprogramming. Additionally, it can explain the mechanisms underlying breast cancer metastasis and drug resistance. Therefore, ITH can become a potential novel therapeutic target. This review summarizes the research progress on the factors that drive ITH as well as its clinical significance in breast cancer.