The aim of this study was to evaluate serial determinations of CYFRA 21-1 in the follow-up of patients treated surgically for non-small cell lung cancer in order to predict the risk of tumour recurrence. Serum levels of CYFRA 21-1 were measured using an immunoradiometric assay (CIS bio) in 57 patients with operable non-small cell lung cancer (NSCLC): 25 with squamous cell carcinoma (SqCC), 20 with adenocarcinoma (AC), 12 with large cell carcinoma (LCC) and 30 with non-malignant lung diseases. Elevated preoperative CYFRA 21-1 levels were identified in 44% of all patients with NSCLC. The diagnostic specificity of the assay was 97%. Positive CYFRA 21-1 levels was observed in 30% of stage I, 33% of stage II, and 55% of stage IIIa. Statistically significant differences were obtained between stages I and IIIa, II and IIIa, but not between stages I and II. During follow-up recurrence was observed in 19 of 57 (33%) NSCLC patients. Recurrence-free survival probability for patients with elevated serum CYFRA 21-1 levels before surgery was 52% (13/25), versus 81% (26/32) for patients with normal serum CYFRA 21-1 levels (p < 0.01). In 15 patients with increased trend for CYFRA 21-1, elevated serum CYFRA 21-1 levels preceded (13 patients) or coincided (2 patients) with the clinical detection of tumour recurrence, providing a predictive value of an increased trend of 87%. In the multivariate analysis the association of the increase of CYFRA 21-1 level with a higher risk of recurrence is statistically significant (p < 0.001).