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Telomerase is a ribonucleoprotein complex composed of the catalytic protein subunit (hTERT) and the RNA template (hTR).  Activation of telomerase activity may be necessary for immortalization of cells.  This enzyme may thus be used as a marker for cell transformation.  However, our understanding of telomerase biology is based largely on the in vitro studies, and the role of telomerase during human oral carcinogenesis in situ is poorly documented.  In the present study, we correlated the telomerase activation and the status of oral carcinogenesis by determining the hTERT messages from paraffin-embedded oral biopsies using real-time reverse transcription (RT)-PCR or in situ RT-PCR.  We found that the majority of squamous cell carcinoma (SCC) tissues contained significantly higher hTERT messages compared to the normal counterpart.  In situ RT-PCR results showed that the hTERT expression was not noted in normal epithelium nor in mild dysplasia, but was detected in moderate dysplasia and in those tissues with higher grade of histopathology: severe dysplasia and invasive carcinoma.  These results indicate that activation of telomerase activity occurs early during human oral carcinogenesis and plays a critical role in the development of human oral cancer.  This work was supported by grants DE14147 and DE 10598 from the National Institute of Dental and Craniofacial Research (NIDCR) at the NIH.           <>