Introduction. Cytokeratin (CK) 19 belongs to type I cytokeratins. CYFRA 21‑1 is an assay which detects the soluble fragment of cytokeratin 19. Objectives. The aim of this study was to compare the CYFRA 21‑1 serum level with cytokeratin 19 expression in tumor tissue. Patients and methods. The CK 19 expression and CYFRA 21‑1 levels were examined in 36 patients with non‑small cell lung cancer (19 men and 17 women). The mean age of the patients was 59.2 ±7.4 years. CK 19 expression was determined by immunohistochemistry using the Monoclonal Mouse Anti‑Human Cytokeratin 19 Clone BA 17 DAKO M 0772. Serum levels of CYFRA 21‑1 were measured using an electrochemiluminescent immunoassay in the analyzer Elecsys 2010 (Roche Diagnostic). Results Positive cytoplasmatic staining of CK 19 was observed in all examined tumor tissues. Weak staining + (CK 1) was found in 12 (33%) patients, medium staining ++ (CK 2) in 16 (44%) patients and strong staining +++ (CK 3) in 8 (22%) subjects. The median CYFRA 21‑1 serum level was 3.19 ng/ml. In 18 patients (50%) CYFRA 21‑1 levels were increased (>3.3 ng/ml). In the group with increased CYFRA 21‑1 serum levels the number of patients with strong CK 19 expression (CK 3) was significantly smaller (1/18 vs. 7/18; χ2 Yatesa 4.02; p = 0.045). Serum CYFRA 21‑1 levels were significantly lower in patients with strong expression of CK 19 (CK 3) (Mann‑Whitney test, p = 0.04). Conclusions. A tendency towards lower serum CYFRA 21‑1 levels is observed in non‑small cell lung cancer patients with strong cytokeratin 19 expression (+++) in tumor cells.