TGFbeta superfamily, antagonizes TGFbeta signaling and counteracts EMT. Here, we have studied the involvement of cancer stem cells (CSCs) in invasiveness and bone metastasis. Furthermore, we evaluated if members of the TGFbeta-superfamily, particularly TGFbeta and BMPs (BMP2, BMP7 and a BMP2/7 heterodimer), can affect bone metastasis formation and whether this putative modification is mediated via CSCs. Our data demonstrate that BMP2/7 heterodimers are more potent inhibitors of TGFbeta-induced Smad signaling than its homodimeric counterparts (BMP2 and BMP7). BMP2/7 strongly inhibited basal and TGFbeta-induced migration of human osteotropic breast and prostate cancer cells (MDA-MB-231, PC3M-Pro4 resp.). Furthermore, TGFbeta significantly increased the size of the CSC subpopulation in both breast and prostate cancer. In contrast, BMPs (particularly BMP2/7) significantly inhibited the size of the CSC subpopulation under basal conditions and antagonized the stimulatory effects of TGFbeta. Strikingly, pretreatment of cancer cells with BMPs in a preclinical model, significantly inhibited the formation and growth of bone metastasis. Collectively, our data support the notion of migrating CSCs in bone metastasis and describe heterodimeric BMP2/7 as a powerful TGFbeta antagonistwith anti-metastatic potency.