We have used in vitro and mouse xenograft models to examine the interaction between breast cancer stem cells (CSC) and bone marrow–derived mesenchymal stem cells (MSC). We show that both of these cell populations are organized in a cellular hierarchy in which primitive aldehyde dehydrogenase expressing mesenchymal cells regulate breast CSCs through cytokine loops involving IL6 and CXCL7. In NOD/SCID mice, labeled MSCs introduced into the tibia traffic to sites of growing breast tumor xenografts where they accelerated tumor growth by increasing the breast CSC population. With immunochemistry, we identified MSC–CSC niches in these tumor xenografts as well as in frozen sections from primary human breast cancers. Bone marrow–derived MSCs may accelerate human breast tumor growth by generating cytokine networks that regulate the CSC population. Cancer Res; 71(2); 614–24. ©2011 AACR.