Metastatic disease contributes to a large proportion of cancer-related deaths, and bone is among the most common sites for metastases for tumors originating in the breast and prostate. The propensity for these cancers to form bone metastases is not completely understood; however, it undoubtedly involves a number of unique characteristics of both the tumor cells and the bone microenvironment. Such an explanation was proposed more than a decade ago with Paget’s “seed and soil” hypothesis, which suggested that meta-static cells are dispersed throughout the body, yet they will only survive and grow upon reaching tissues that are optimal for their growth (reviewed in ref. 1).