The exact diagnosis of malignant pleural effusions (PE) is difficult and often requires combined procedures, because the cytological examination of pleural fluid does not detect tumoral cells in 40% of malignant effusion cases. The aim of this study was to analyze microsatellite alterations (MA) in malignant PE and to determine their diagnostic value as an additional test to cytological examination. The increase in cell-free DNA levels was also evaluated as a signal of probable malignancy.