Osteoclasts (OCs) and dendritic cells (DCs) induce expansion and functional activation of NK and T cells. When comparing OCs with DC-induced activation in NK cells, OCs induced significantly higher cell expansion and functional activation of NK cells as compared to DCs, either from healthy individuals or those obtained from cancer patients. However, no differences could be seen in the levels of cell expansion and functional activation in T cells activated by OCs or DCs, either from healthy individuals or those from cancer patients. OCs selectively expanded and activated CD8 + T cells, whereas DCs expanded and activated CD4 + T cells. In addition, both allogeneic and autologous OCs induced similar levels of cell expansion and functional activation of NK and T cells. Together, these findings highlighted the essential roles of OCs in expanding and activating the cytotoxic effectors of NK, and CD8 + T cells, and demonstrated several differences when compared to the effect of DCs.