Although it has long been known that a pathologically activated CXC12/CXCR4 axis is significantly associated with increased proliferation or enhanced metastatic potential in a variety of human neoplasms [10,77,78], the first evidence of CXCR4 mutations dates back to 2005, when Schuller et al. first identified two mutations—one germline (A157C) and one somatic (C414T)—in human medulloblastoma, a frequent malignant brain tumor in childhood [79]. The gene discussed is CXCR4; the disease is medulloblastoma.