Here, we report that the CXCL13/CXCR5 interaction promotes the migratory and invasive potential of human osteosarcoma cells, which in turn mediates the phospholipase C β (PLCβ), protein kinase C α (PKCα), c-Src, and nuclear factor-κB (NF-κB) pathways. Here, CXCR5 is linked to osteosarcoma.