This study used an immunohistochemical technique to examine the expression of human telomerase reverse transcriptase (hTERT) protein in 82 specimens of OSCC, 116 specimens of oral epithelial dysplasia (OED), and 21 specimens of normal oral mucosa (NOM). The cytoplasmic and nuclear hTERT staining intensity (SI; 0, no staining; 1, weak; 2, moderate; 3, strong), labeling indices (LIs, defined as the percentage of positive cells in total cells), and labeling scores (LSs, defined as LI x SI) in OSCC, OED, and NOM samples were calculated and compared among groups. The correlation between the cytoplasmic or nuclear hTERT LS in OSCCs and clinicopathological parameters or survival of OSCC patients was analyzed statistically. The mean cytoplasmic hTERT LSs increased significantly from NOM (87+/-17%) through OED (95+/-18%) to OSCC samples (114+/-33%, p=0.000). The mean nuclear hTERT LSs also increased from NOM (80+/-14%) to OED (91+/-20%) and then decreased to OSCC samples (86+/-35%) with no statistically significant difference among the 3 groups. A significant correlation was found between the higher mean cytoplasmic hTERT LSs and OSCCs occurring in male patients (p=0.023), with larger tumor sizes (T3 and T4, p=0.048), with more advanced clinical stages (stages 3 and 4, p=0.033), or from patients with areca quid chewing (p= 0.029), cigarette smoking (p=0.027), or alcohol drinking habit (p=0.025). In addition, OSCC patients with nuclear hTERT LSs greater than 100% were prone to have a higher recurrence rate (p=0.044) and a lower 5-year survival rate (p=0.011). Our results indicate that the increased expression of hTERT protein is an early event in oral carcinogenesis and hTERT may be a biomarker for OSCCs. Measuring the amount of cytoplasmic or nuclear expression of hTERT in OSCC samples may predict the oral cancer progression, recurrence, and prognosis in Taiwan.