The CYFRA 21-1 assay is a test that has been developed recently for detection of a cytokeratin 19 fragment in serum. A diagnostic role for CYFRA 21-1 has already been proposed. The question of whether this marker is prognostically significant is important in clarifying the role of CYFRA 21-1 in clinical practice. The aim of this study was to evaluate the prognostic significance of elevated preoperative CYFRA 21-1 levels in patients with resected primary squamous-cell lung cancer (SqCC). Serum levels of CYFRA 21-1 were measured using an immunoradiometric assay (CIS bio) in 91 patients with operable SqCC. Survival and disease-free survival curves related to initial levels of this marker were estimated using the Kaplan-Meier method. In the univariate analysis the log-rank test and the log-rank test for trend were used. In the multivariate analysis the stratified log-rank test and the proportional hazard model were used. Elevated preoperative CYFRA 21-1 levels were identified in 55% of patients with SqCC. The number of patients with elevated levels of this marker increased with TNM stage (P = 0.0001). In univariate analysis elevated levels of CYFRA 21-1 were significantly associated with poor overall survival (P < 0.00005) and with disease-free survival (P < 0.00005). In multivariate analysis elevated levels of this marker were also found to be associated with poor overall and disease-free survival (P = 0.01 and P = 0.003 respectively). In conclusion, CYFRA 21-1 may be an independent prognostic parameter of survival and tumour relapse in SqCC and may be useful in identifying resected SqCC patients at high risk of treatment failure.