In the present study, we aimed to: i) detect the expression of CXCR4 and CXCR7 in two OS cell lines; ii) investigate the roles of the CXCL12-CXCR4 axis and AMD3100 in OS cell survival and migration in vitro; iii) identify downstream pathways regulated by CXCL12/CXCR4 in OS; and iv) assess the effect of AMD3100 on primary tumor growth and lung metastasis in an OS animal model. This evidence concerns the gene CXCL12 and neoplasm.