We evaluated the correlation between serum cytokeratin 19 fragment (CYFRA 21-1) and tissue polypeptide antigen (TPA) levels in 57 non-small cell lung cancer patients. There was a significant correlation between serum CYFRA 21-1 and TPA levels for each clinical stage and TNM (T, primary tumor; N, regional lymph node involvement; M, occurrence of distant metastasis) subcategory (range of r-value = 0.809-0.998, P < 0.01). High correlations between serum CYFRA 21-1 and TPA levels were found in eight patients both before and after the surgery, in 22 patients before and after chemotherapy and in another 27 patients who could not complete the scheduled chemotherapy (range of r-value = 0.856-0.998, P < 0.0001). However the positive rate of CYFRA 21-1 was higher than that of TPA (61% vs. 53%, P < 0.05). CYFRA 21-1 would yield better diagnostic results for non-small cell lung cancers than TPA, though these tumor markers are both cytokeratin-associated tumor markers.