In this context, whereas the classical “secreted” OPN has always been associated to a tumor-promoting activity, and, in line, in our study it sustains the aggressiveness of an already established lymphoma cell line, by identifying intracellular OPN as a relevant “brake” in the process of DLBCL lymphomagenesis, this work raises a “warning” in considering OPN, straightforwardly, a bad prognostic factor or a potential therapeutic target. The gene discussed is SPP1; the disease is lymphoma.