Deregulated transcription factor Paired box gene 5 (Pax-5) expression has been implicated in B-cell lymphoma in human disease. Proviral Integration of Moloney virus 2 (Pim-2) kinase may play a role in apoptosis and chemotherapy resistance. We characterized the expression of Pax-5 and Pim-2 in mature B-cell lines and 293T cells transfected with human isoforms of Pax-5. By quantitative real-time polymerase chain reaction (qRT-PCR), we showed that Pax-5 isoforms significantly increased Pim-2 mRNA expression in 293T cells and that mRNAs for both Pax-5 and Pim-2 were two-fold significantly expressed in mature malignant B-cells. Western blot analysis showed that Pim-2 protein expression was increased in 293T cells transiently transfected with human isoforms of Pax-5 and that Pax-5 isoforms and Pim-2 proteins were expressed in mature B-cell lines. By electrophoretic mobility shift analysis, we showed that Pax-5 isoforms were able to bind to the Pim-2 promoter region. Taken together, these results suggest that Pax-5 may act as a transcription factor to modulate the expression of Pim-2 and that both proteins may play a role in the oncogenesis of mature B-cell lymphoma.