In many cases of exudative pleural effusion, the results were not conclusive even after (repeated) thoracocentesis; that mostly need confirmatory pleural tissue biopsy. Pleural biopsy is indicated to define the etiology of pleural diseases; the biopsy obtaining techniques are variable starting from the older ones such as blind pleural biopsy reaching the newer techniques such as image guided pleural biopsy and thoracoscopy guided pleural biopsy. Exudative pleural effusions result from local or systemic diseases that directly injure the pleural surface. Although a wide variety of processes can result in exudative pleural effusions, the two main etiologic categories are inflammatory and neoplastic disease. The pleural fluid cytology will be positive on the first specimen submitted in >50% of patients with pleural malignancy. Almost all adenocarcinomas will be diagnosed with cytology. Cytology may assist the diagnosis of several nonmalignant conditions e.g., esophageal rupture by detection of oral squamous cells or meat fragments (striated muscle) in pleural fluid.