This review documents a practical approach to the pathological diagnosis of pleural malignant mesothelioma based on the closed needle biopsy and effusion cytology, thus avoiding the need to resort to open surgery. Tissue diagnosis is often difficult, and the pathologist's opinion may be influenced by a consideration of three factors: the clinical setting; the adequacy and availability of specimens; and the criteria for assessment and interpretation of these. The level of confidence with which a tissue diagnosis of mesothelioma can be established using limited material depends on there being an appropriate clinical background including a history of asbestos exposure. Without this, the diagnosis should be a qualified or tentative one. For an adequate tissue sample to be obtained, the closed needle biopsy procedure is best performed by an experienced operator. All aspirated pleural effusions should be forwarded for cytological evaluation. In addition to conventional morphological studies, adequate samples permit ancillary tests to be carried out. A combined interpretive approach utilizing both histopathology and cytology is recommended in order to increase the accuracy of the diagnosis.