We determined: (i) a direct correlation between circulating CLL monocytes expressing CD16 and the levels of bone erosion; (ii) that the treatment of healthy monocytes with CLL-conditioned medium up-regulated the expression of CD16, RANK and RANKL and increased the rate of osteoclast formation; (iii) that monocytes polarized toward the M2 phenotype showed higher CD16 expression than M1 and were more prone to differentiate into osteoclasts. Here, FCGR3A is linked to B-cell chronic lymphocytic leukemia.