Multiple myeloma（MM）develops and expands almost exclusively in the bone marrow, and generates devastating bone destruction. MM cells produce a variety of cytokines, including MIP‐ １, to stimulate RANK ligand-mediated osteoclastogenesis and extensively resorb bone. Besides enhancing bone resorption, MM cells suppress osteoblastic differentiation from bone marrow stromal cells, leading to extensive bone destruction with rapid loss of bone. The overproduction of inhibitors for the canonical Wingless-type（Wnt）signaling pathway, including DKK‐１, sFRP‐２ and sclerostin, significantly contributes to the suppression of osteoblastogenesis and bone formation in MM. MM cells alter through bone destruction the microenvironment in bone where they colonize, which in turn favors MM tumor growth and survival, thereby forming a progressive vicious cycle between tumor expansion and bone destruction in MM. MM is still difficult to be cured despite the recent implementation of new agents, and its bone disease also remains a significant clinical problem. Further elucidation of the molecular mechanisms of the tumor-bone interactions and tumor growth in the bone microenvironment will provide us with new approaches that have a real impact on both bone disease and tumor progression in MM.