CYFRA 21-1 was evaluated in 115 untreated patients with malignant pleural effusions (96 with primary lung cancer and 19 with non lung cancer) and 99 patients with benign pleural effusions. The levels of pleural fluid CYFRA 21-1 were from 1 to 385 times higher than those in serum, in all the examined patients. The mean level of pleural fluid CYFRA 21-1 was significantly higher in cancer patients than in patients with benign pleural effusion (96.1 ng/ml vs 26.2 ng/ml, p < 0.001). At 92% specificity for benign pleural effusion (> 50 ng/ml) the overall sensitivity of CYFRA 21-1 in malignant pleural effusions was 69.6%. When the histology was considered the highest sensitivity was found in squamous cell lung cancer (90%), followed by adenocarcinoma cell lung cancer (74%), non lung cancer (54%) and small cell lung cancer (25%). These results indicate that CYFRA 21-1 could be a useful pleural fluid marker in discriminating benign from malignant pleural effusion and particularly from those due to squamous and adenocarcinoma cell lung cancer.