The current study of 879 patients with de novo DLBCL identified 48 (5.5%) CD5+ patients, associated with higher frequencies of >1 ECOG performance status, BM involvement, CNS relapse, ABC subtype, Bcl-2+, and STAT3 activation whereas with lower frequencies of CD30+, SSBP2+, and MYC mutations. This evidence concerns the gene TNFRSF8 and diffuse large B-cell lymphoma.