Background:Head and neck cancer including oral cancer is considered to develop by accumulated genetic alterations and the major pathway is cancerization from lesions such as intraepithelial dysplasia in oral leukoplakia and erythroplakia. The relationship of proliferation markers with the grading of dysplasia is uncertain. The involvement of EBV in oral carcinogenesis is not fully understood. Aim: The present study was designed to investigate the role of EBV and DNA Topoisomerase IIu (DNA-Topo IIu) during oral carcinogenesis and to examine the prognostic significance of these protein expressions in OSCCs. Methods: Using specific antibodies for EBV and DNA-Topo IIu, we examined protein expressions in archival lesion tissues from 16 patients with oral epithelial dysplasia, 22 oral squamous cell carcinoma and 20 normal oral mucosa by immunohistochemistry. Clinical information was obtained through the computerized retrospective database from the tumor registry. Results: DNA-Topo IIu was expressed in all examined specimens. Analysis of Variance ANOVA revealed highly significant difference (P0.05) in inferior surface of tongue and in hard palatal tissues. Significant differences were observed between OEDs and NSE (P