The oncogenic transcription factor PAX5 is an important developmental regulator and is implicated in the pathogenesis of several malignancies. The PAX5 gene is involved in medulloblastoma, non-Hodgkin's lymphoma, transitional cell carcinoma of the bladder, neuroblastoma, breast cancer and SCC. In the current study, to determine the potential involvement of PAX5 in oral squamous-cell carcinoma (OSCC) and leukoplakias, we evaluated the status of PAX5 mRNA and protein expression in OSCC cell lines, human primary OSCCs, and leukoplakias by real-time quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry. A significant increase in PAX5 expression was observed in all OSCC-derived cell lines examined compared to human normal oral keratinocytes (HNOKs). In immunohistochemistry, 78% of tumors and 42% of leukoplakias examined were positive for PAX5, while no immunoreaction was observed in corresponding normal tissues. The results suggest that PAX5 plays an important role during oral carcinogenesis, especially in the early stage, and that the gene may have potential as a biomarker and therapeutic target for OSCC.