Recently, we have demonstrated that INSL3 is important for bone metabolism, and in this study we analyzed the possible role of the cognate hormone relaxin on human osteoclasts. In fact, previous studies showed an effect of relaxin on peripheral blood mononuclear cells (PBMCs), the precursors of osteoclasts. Analysis of the expression of the relaxin receptor RXFP1 and RLN-2 mRNA in primary cell cultures of human osteoclasts obtained from PBMCs showed by reverse transcriptase PCR and immunofluorescence only the presence of RXFP1 transcripts. Analysis of the in vitro effects of relaxin on osteoclastogenesis showed that relaxin is able alone to induce the differentiation of PBMCs into mature osteoclasts. This study shows, for the first time, that relaxin has an effect on bone metabolism, facilitating the differentiation of osteoclasts. A possible role for relaxin in osteolytic bone metastasis is also proposed.