In this study, we present the following discoveries: (1) CCDC50 is increased in ABC-DLBCL and associated with poor prognosis, (2) CCDC50 stabilizes c-Myc protein in a PI3K/AKT/GSK-3β dependent manner, leading to the proliferation of ABC-DLBCL, and (3) DLBCL-derived CCDC50-positive exosomes in plasma effectively distinguish DLBCL subtypes and predictes patient severity. Here, GSK3B is linked to diffuse large B-cell lymphoma.