In recent years, the onset of whole-genome sequencing has revealed CXCR4 as one of the most frequent somatic mutations identified in the indolent form of B-cell non-Hodgkin lymphomas (B-nHL), although their relevance for clinical presentation and overall survival, as well as their relationship with resistance to chemotherapy, are still unsolved issue. This evidence concerns the gene CXCR4 and B-cell non-Hodgkin lymphoma.