Osteoclasts are bone-resorbing multinucleated cells derived from the monocyte–macrophage lineage. Bone-forming osteoblasts play a role in the formation of osteoclasts. Osteoblasts/stromal cells express two cytokines essential for osteoclastogenesis: receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Using RANKL and M-CSF, osteoclasts can be induced from monocyte–macrophage lineage cells even in the absence of osteoblasts. We describe here methods for the identification of osteoclasts formed in vitro.