In conclusion, we developed a new molecular classification to divide CNS DLBCL into CDP and non-CDP groups based on the mutational status of CD79B and PIM1. CNS DLBCL patients with PIM1 and/or CD79B mutation had favorable long-term survival after HD-MTX-based chemoimmunotherapy. This evidence concerns the gene PIM1 and diffuse large B-cell lymphoma of the central nervous system.