Runx2 is an osteoblast-specific transcription factor, which regulates osteoblast differentiation and bone formation. In breast cancer, Runx2 activates expression of bone matrix and adhesion proteins, matrix metalloproteinase and angiogenic factors that has long been associated with metastasis. Runx2 forms co-regulatory complexes with some co-activator and co-repressor proteins that are organized in subnuclear domains to regulate gene transcription and mediates the responses of cells to signaling pathways activate in breast tumors. In addition, Runx2 could also interact with the estrogen receptors in some extent to discharge the effect of estrogen and its receptors on the development of breast cancer. This article mainly summarizes Runx2's roles in breast carcinoma and its interaction with estrogen receptors.