Interleukin-34 (IL-34) is a cytokine which binds and activates the M-CSF receptor (M- CSFR). Consequently, IL-34 shares functional similarities with M-CSF such as the regulation of the myeloid cell differentiation. We recently demonstrated that IL-34 had a central role in osteosarcoma (OS) by modifying the local tumour microenvironment, promoting the formation of new blood vessels, and attracting M2-type macrophages to the tumour site (Segaliny et al, 2015). Soluble factors and extracellular vesicles (EV’s) are the two main protagonists of the dialog between cancer cells and their microenvironment (Hiraga & Yoneda, 2005). This work aims to better characterize the functional communications between OS cells and their environment with a specific focus on EV’s and the contribution of IL-34 in this dialog.