The most critical form of mesothelioma is the malignant form. Known as malignant mesothelioma, the primary causal factor is asbestos infection. According to the US National Cancer Institute, "Malignant mesothelioma is a disease in which cancer (malignant) cells are found in the sac lining the chest (the pleura), the lining of the abdominal cavity (the peritoneum) or the lining around the heart (the pericardium)."

Mesothelioma can be classified into three types pleural mesothelioma, peritoneal mesothelioma and pericardial mesothelioma. Pleural mesothelioma refers to a cancer of the lining of the lung (pleura), peritoneal mesothelioma refers to a cancer of the abdominal cavity (peritoneum) lining, and pericardial mesothelioma is a cancer that occurs in the lining that surrounds the heart (pericardium). The subtypes of mesothelioma are of three basic types, one very aggressive, one least aggressive, and one lying between the two extremes.

Malignant mesothelioma can be diagnosed through several imaging techniques. These imaging techniques enable physicians to assess mesothelioma. Once mesothelioma is suspected, patients are advised to undergo several tests, like X-ray, Computed Tomography (CT) scan, Magnetic Resonance Imaging (MRI) scans, and Positron Emission Tomography (PET) imaging. The physician may also like to undertake special mesothelioma tests like thoracoscopy, peritoneoscopy and biopsy.

Learning about the stage of mesothelioma is a critical factor that helps physicians to decide the treatment plan. If the cancer is confined to the pleura, mesothelioma is considered localized. If the cancer spreads beyond the pleura and to other parts of the body such as the lungs, abdominal cavity, lymph nodes and the chest wall, mesothelioma is considered to be in an advanced stage.

The oft used and the oldest system for determining the stages of mesothelioma is the Butchart System. The Butchart System is based on the extent of the primary tumor mass available in a patient. This system divides mesothelioma into four stages. The TNM system, a slightly advanced system over the Butchart System, determines staging through variables of tumor in mass and the spread, the lymph node involvement and metastasis. However, the latest system is known as the Brigham System, where staging is done as per the respectability and lymph node involvement. In spite of such modern techniques, a definitive diagnosis of mesothelioma still remains possible through fluid diagnosis and tissue biopsy.