The transcription factor Runx2 is essential for the formation of the skeleton. It has therefore primarily been considered as a specific regulator of bone genes. However, mice containing a LacZ insertion at the Runx2 locus also revealed expression in the nascent mammary epithelium. Reports of Runx2 expression in breast cancer cell lines, combined with the fact that breast cancers preferentially metastasise to bone, have also hinted at a potential role for Runx2 in the formation of bone metastasese. These initial observations have prompted further analysis of Runx2 function in mammary epithelial cells and recent findings have demonstrated that Runx2 does indeed contribute to the ability of metastatic breast cancer cell lines to form osteolytic bone lesions. In addition, evidence is accumulating that Runx2 has a role in the regulation of normal mammary gland gene expression and recent data demonstrate that it regulates transcription of the mammary gland-specific gene, β-casein. In this article I discuss recent advances that link Runx2 with normal mammary epithelial cell function and the development of bone metastasese in breast cancer. © 2005 Wiley-Liss, Inc.