Although further studies are still needed to better evaluate the role of CXCL12 and CXCR4 in the process of NSCLC metastatic spread to brain, their use as predictive markers of metastasis in brain (with or without extracranic sites) may be clinically relevant for the invalidating consequences on patient’s autonomy and quality of life, and the opportunity to implement radiological surveillance. The gene discussed is CXCR4; the disease is non-small cell lung carcinoma.