Our results confirm the expression of CXCR4 in both chondrosarcoma tissue and cell lines and also show that CXCR4 expression was higher in high grade tumors, that hypoxia and HIF-1a enhance CXCR4/SDF1 mediated invasion through upregulation of CXCR4 expression, and that CXCR4/SDF1 signaling increases invasion through ERK mediated increase in MMP1 expression and activity. The gene discussed is CXCR4; the disease is chondrosarcoma.