Protein kinase C-beta II (PKC-beta II) expression has been reported to indicate inferior prognosis in diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-based chemotherapy. This study compared prognostic significance of immunohistochemically determined PKC-beta II expression in de novo DLBCL treated with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) chemotherapy with and without rituximab. Outcomes were assessed in 80 consecutive patients, 48 treated with CHOP, and 32 with rituximab plus CHOP (R-CHOP). PKC-beta II expression correlated with inferior overall survival (OS) and progression-free survival (PFS) in CHOP-treated patients with low-risk International Prognostic Index (IPI) disease (0-2 adverse factors), but not in the overall patient group unstratified by IPI. PKC-beta II expression correlated with inferior OS and PFS in R-CHOP-treated patients unstratified by IPI status. Immunohistochemically demonstrated PKC-beta II expression thus identified patient subgroups where alternative treatment strategies may confer superior outcome. We now report that PKC-beta II expression has prognostic significance not only for CHOP therapy in low-risk IPI disease, but also for all patients receiving CHOP plus rituximab.