Telomerase activity is considered to be a diagnostic marker of malignancy since most malignant cells express this activity and most somatic cells do not. However, the detection of telomerase activity is rather complicated and is affected by many factors. Recently, human telomerase components were cloned and found to consist of 3 subunits. We assessed which component of telomerase best correlates with malignancy in order to study the possibilities for developing a new diagnostic marker. Telomerase activity was measured by a telomeric repeat amplification protocol (TRAP) assay, and the telomerase components hTR, hTRT-mRNA and TP1-mRNA were detected by the reverse transcriptase-polymerase chain reaction (RT-PCR). Twenty-five of 26 oral malignant lesions, 9 of 22 benign lesions and none of 19 normal control tissues exhibited distinct telomerase activity. hTR and TP1-mRNA expression levels were detected in all malignant lesions and normal control tissues and had no significant correlation with the telomerase activity results. In contrast, hTRT-mRNA expression was closely associated with telomerase activity. All lesions expressing hTRT were telomerase positive. In addition, some samples of dysplastic lesions, benign tumors, lichen planus and normal mucosa exhibiting poor telomerase activity revealed weak expression of hTRT. Expression levels of hTRT-mRNA positively correlated with clinical and pathological findings. Detection of hTRT-mRNA by RT-PCR appeared to be more sensitive for telomerase than measurement of telomerase activity by the TRAP assay. Detection of hTRT-mRNA may provide information useful in the diagnosis of oral malignancies.