Together, these studies illustrate a continuum of microenvironmental dependence in MM: while BM-localized myeloma relies on ROR2-mediated adhesion and PI3K/AKT signaling to interact with stromal and mesenchymal elements, EMD appears to exploit a distinct strategy, namely, the remodeling of the immune niche to suppress antitumor responses. The gene discussed is ROR2; the disease is plasma cell myeloma.