A positive cytology result in pericardial fluid is the gold standard for recognition of malignant pericardial effusion. Unfortunately, in 30-50% of patients with malignant pericardial effusion cytological examination of the pericardial fluid is negative. Tumor marker assessment in pericardial fluid may help to recognize malignant pericardial effusion. The aim of our study was to estimate the value of CYFRA 21-1 and CEA measurement in pericardial fluid for the recognition of malignant pericardial effusion. To our knowledge this is the first study on CYFRA 21-1 assessment in pericardial effusion. The examined group consisted of 50 patients with malignant pericardial effusion and 34 patients with non-malignant pericardial effusion. Median CEA concentrations in malignant pericardial effusion and non-malignant pericardial effusion were 80 ng/mL (0-317) and 0.5 ng/mL (0-18.4), respectively (p<0.001). Median CYFRA 21-1 concentrations in malignant pericardial effusion and non-malignant pericardial effusion were 260 ng/mL (5.3-10080) and 22.4 ng/mL (1.87-317.6), respectively (p<0.001). The optimal cutoff value for CYFRA 21-1 in pericardial effusion was 100 ng/mL. CYFRA 21-1 >100 ng/mL or CEA >5 ng/mL were found in 14/15 patients with malignant pericardial effusion and negative pericardial fluid cytology. We therefore strongly recommend the use of CYFRA 21-1 and/or CEA in addition to pericardial fluid cytology for the recognition of malignant pericardial effusion.