Malignant mesothelioma of the pleura is a disease that requires a biopsy procedure for a definitive diagnosis. In the past, closed pleural needle biopsy (CPNB) has given poor yields due to the small amount of tissue obtained, and the patient has subsequently been subjected to a diagnostic thoracotomy. In recent years, the availability of more accurate histopathologic tests have enabled the pathologist to make a diagnosis more easily on samples obtained at CPNB. In this retrospective study of 20 consecutive cases of malignant mesothelioma of the pleura diagnosed between 1980 and 1990, we found that a blind CPNB was diagnostic in five of seven procedures and CT-guided CPNB was diagnostic in five of six procedures. An open pleural biopsy (OPB) was diagnostic in ten of ten procedures performed. There were no complications associated with any of the CPNB procedures. We conclude that CPNB is a safe and effective manner of diagnosing malignant mesothelioma of the pleura, and should be attempted prior to OPB.