Background: Primary mediastinal large B cell lymphoma (PMBL) is an aggressive non-Hodgkin’s lymphoma (NHL) and has distinct clinico-pathologic as well as molecular characteristics. Mutation of P53 has been reported in PMBL in 13-16% of cases in the previous studies. The role of Retinoblastoma (Rb) gene, another tumor suppressor gene, in this type of lymphoma genesis has not been established yet. Previous studies showed the absence of bcl-2 gene expression in PMBL. Materials and Methods: To determine the pathogenic roles of these two tumor suppressor genes and bcl-2, an anti - apoptotic factor, we analyzed formalin fixed paraffin embedded blocks of ten cases of PMBL by Immunohistochemical staining (IHC). Results: Six cases were P53 positive, and 8 cases were strongly positive for Rb. There were also strong cytoplasmic positivity for bcl-2 antibody in 6 cases. Two P53 positive cases were negative for bcl-2, and nuclear staining for P53 and positive reaction for bcl-2 were detected concurrently in 4 cases. Conclusion: Our study showed high Rb protein expression (80%) in PMBL, and it implies cell cycle derangement. Rb protein does not seem to be involved in pathogenesis of PMBL. Extensive P53 expression by tumor cells correlates with clinico-pathologic features of PMBL. We observed bcl-2 over expression in 60% of the cases; thus, we suggest the role of this factor in pathogenesis of PMBL. The discrepancy between P53 mutation and bcl-2 over expression in previous studies and the study at hand can be explained by different methods of detection, technical factors, and various fi