A diagnosis of mesothelioma from fluid is many times inconclusive. Given this fact, diagnostic surgery becomes a necessary next step in confirming and staging mesothelioma.

There are four different type of prsedures:

1. Thoracoscopy enables a physician to evaluate the pleural cavity and to conduct multiple tissue biopsies under direct vision. In up to 98% of cases, a definitive diagnosis can be obtained. Often, chemical pleurodesis aimed at relieving the accumulation of fluid in the intrapleural space, can be accomplished during the same procedure. It is also possible to gauge the extent of the tumor, and make a determination of surgical resectability. While less invasive than an open biopsy, it can only be performed on patients where tumor has not obliterated the pleural space.
2. VATS, or video-assisted thoracic surgery is an alternative to thoracoscopy, although because of its more invasive nature, concerns of tumor seeding increase. By utilizing small incisions, the physician can view the pleural space with the assistance of a camera, and obtain sufficient tissue samples for analysis by a pathologist. Extent of the tumor (i.e., pleural involvement, chest wall invasion) may also determined, and recommendation as to the type of debulking procedure necessary can be made at this time.
3. Mediastinoscopy is sometimes used as an aid in staging extent of disease when enlarged nodes are seen using imaging techniques.
4. Laproscopy is used in mesothelioma patients in cases where imaging techniques suggest possible invasion of the tumor through the diaphragm. This information can be important in evaluating a patient for potential pleurectomy or extrapleural pneumonectomy.