Lung cancer is the most common cancer worldwide with 900,000 new cases each year in men and 330,000 in women, being also the major cause of death from cancer. In Greece about 4,000 persons die every year due to lung carcinoma. One of the major problems in the follow up of these patients is the difficulty of early detection of recurrent disease. Tumor markers are of particular interest in this respect. Cytokeratines, especially fragment 19, are specified epithelial tissue-proteins that show increased levels in patients with carcinomas. CYFRA 21-1 assays determine the serum cytokeratin 19 fragment. The aim of our study was to evaluate the importance of serum CYFRA 21-1 studied by immunoradiometric assay in patients with various types of lung cancer after surgery or chemotherapy. Ninety-six consecutive patients were studied during a two years period. Forty-five of them had small cell lung cancer (SCLC) and 51 had non-small cell lung cancer (NSCLC). Moreover, 52 healthy individuals were studied to estimate the cut off value of CYFRA 21-1. Increased serum levels of the marker were found in patients with lung cancer compared to controls (P<0.001). The cut off value was estimated as 3.3 ng/ml with 96% specificity. Before the treatment there was no difference in the sensitivity of CYFRA 21-1 for patients with SCLC (21/45 patients had increased CYFRA 21-1 levels, 47%) and for patients with NSCLC (27/51 had increased levels, 52%). Also, before treatment there was a higher sensitivity in NSCLC than in SCLC and especially in SCC among other histotypes of NSCLC when different stages of the disease were compared. Patients with extended disease, metastatic or recurrent disease had also more increased levels of the marker (P<0.001). One month after surgical ablation of the primary lung lesion, 28/58 patients showed a drop in the levels of the marker as an indication of the tumor ablation. From the 58 operated patients 35 relapsed and 31/35 showed an increase in CYFRA-21-1 levels with a sensitivity of 92% and specificity of 95%. From the 38 patients that underwent chemotherapy treatment, 24 had a depravation of the disease and 21/24 had a great increase of serum CYFRA 21-1 with a sensitivity of 89% and specificity of 94%. In conclusion, CYFRA 21-1 is a useful tumor marker before and after surgical treatment in lung cancer.