Malignant pleural effusions (MPEs) are a challenging public health problem, causing significant morbidity and often being the first presenting sign of cancer. Pleural fluid cytology is the most common method used to differentiate malignant from non-malignant effusions. However, its sensitivity reaches 50-70% and depends on the experience of the cytologist, the tumor load, and the amount of fluid tested. Therefore, diagnostic inaccuracy and a high incidence of false negatives may endanger patients with clinical mistreatment and mismanagement.