The critical contribution of chemokine receptor-mediated signaling pathways to cancer cell hallmarks has been robustly established and was further emphasized by the pro-oncogenic signaling driven by GOF mutations that have been identified for CCR4 and CCR7 in ATTL and for CXCR4 in the Waldenström macroglobulinaemia; the latter mutations being similar to those inherited causing the WHIM syndrome and promoting the oncogenic program in HPV-infected keratinocytes. The gene discussed is CXCR4; the disease is Waldenstrom macroglobulinemia.