In recent years, elucidation of the molecular mechanisms responsible for EBV− DLBCL has enabled the identification of multiple mutational hotspots—including MYD88, CD79A, and CARD11—that promote B-cell receptor (BCR) and/or Toll-like receptor (TLR)-mediated activation of NF-kappa B signaling. This evidence concerns the gene BCR and diffuse large B-cell lymphoma.