Using a preclinical murine model of OSCC, we sought to determine: (i) whether pharmacological inhibition of CXCR4 with AMD3100 attenuates mandibular bone destruction; (ii) whether this effect is mediated through the suppression of osteoclast activation; and (iii) whether CXCR4 inhibition impairs the EMT process in cancer cells. The gene discussed is CXCR4; the disease is cancer.