Objective: The clinical importance of preoperative CYFRA 21-1 measurement in early-stage non-small cell lung cancer (NSCLC) is still unclear. The aim of this study is to clarify the prognostic value of preoperative CYFRA 21-1 levels in clinical stage (c-stage) I NSCLC. Methods: The records of 101 c-stage I NSCLC patients who had undergone complete resection were analyzed to correlate preoperative CYFRA 21-1 levels to both the pathologic factors of resected specimens and postoperative outcomes. The cut-off value was set at 3.5 ng/ml. Results: Six cases (5.9%) showed high CYFRA 21-1 (>= 3.5 ng/ml). The 5-year survival of normal and high CYFRA 21-1 groups was 83.3% and 50.0%, respectively. Patients with high CYFRA 21-1 had significantly poor outcomes (P = 0.006). In univariate analysis, preoperative serum CYFRA 21-1 level, pT, pN, and p-stage were significantly associated with prognosis. Multivariate analysis showed that only CYFRA 21-1 level was retained as an independent prognostic factor (relative risk = 9.79, P = 0.002). Conclusions: CYFRA 21-1 is an independent predictor of poor outcome for c-stage I NSCLC. Elevated preoperative CYFRA 21-1 levels in early-stage NSCLC may indicate a subgroup at high risk of early death, which has the potential for better survival with additional systemic chemotherapy. (c) 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.