The S100 family of proteins has been shown to bind to the RAGE and Toll-like receptor 4 (TLR4) receptors to mediate tumor growth and survival.18,19 The cell surface protein CD44 has also been implicated in S100A4-induced cytoskeletal changes in melanoma.20 Therefore, we explored whether S100A4 utilizes one of these surface receptors for osteoclastogenesis. Here, TLR4 is linked to melanoma.