Activation of telomerase plays a critical role in unlimited proliferation and immortalization of cells. The purpose of this study was to evaluate the significance of human telomerase reverse transcriptase catalytic subunit (hTERT) as a prognostic marker. The expression of hTERT in a large population of 153 patients with stage I non-small cell lung cancer was analyzed using the in situ hybridization technique. We found that diffuse and clear hTERT expression was present in 51 (33%) of 153 patients. Kaplan-Meier analysis showed that hTERT expression was associated with shorter overall survival (P = 0.04), shorter disease-specific survival (P = 0.03), and shorter disease-free survival (P = 0.02). Multivariate analysis confirmed this independent prognostic value of hTERT expression. Our results indicated that hTERT mRNA expression is associated with malignant tumor progression and poor outcome. hTERT may serve as a useful marker to identify patients with poor prognosis and to select patients with early-stage non-small cell lung cancer who might benefit from adjuvant treatment.