Receptor tyrosine kinases MET and RON (MST1R) form non-covalent complexes on the cell surface, a critical step in tumor progression. A recent study suggested a prognostic role for MET expression in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to examine the impact of MET and RON expression in uniformly treated DLBCL patients. The expression of MET and RON was retrospectively examined by immunohistochemistry in 120 DLBCL patients treated with rituximab combined with a CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone). The median follow-up time was 42.5 months (range, 1-89 months). Thirty-two (26%) and 30 patients (25%) expressed MET or RON, respectively. Seventy-five patients (62.5%) were negative for both MET and RON (MET-RON-). MET negativity was associated with worse overall survival (P = 0.029). In multivariate analysis, negativity for both MET and RON (MET-RON-) was strongly associated with inferior overall survival (P = 0.008). Interestingly, the MET-RON- phenotype retained its prognostic impact after subgroup analysis according to the international prognostic index or by the cell of origin by immunohistochemical algorithm by Choi et al. This study suggests that the MET-RON- phenotype is an independent prognostic factor in DLBCL patients receiving R-CHOP, and may identify a subgroup of DLBCL patients who require more intensive therapy.