Although the onset of the disease is insidious, once established, malignant mesothelioma progresses rapidly by local extension to the pericardium, mediastinum, and contralateral pleura. Pain and dyspnea become progressive. Extension to other thoracic structures creates superior vena cava syndrome, hoarseness, and dysphagia. Abdominal extension is common and involves the abdominal lymph nodes and organs. Mesothelioma is associated with the development of paraneoplastic disorders, which include thrombocytosis, hemolytic anemia, Disseminated Intravascular Coagulation, and migratory thromboplebitis. Tumor recurrence rate after surgery is as high as 50%.

Death results from respiratory failure and local extension to other organs. Untreated mesothelioma is fatal in 4-8 months. Patients who receive multimodality care may survive 16-19 months. The five-year survival rate is less than 5%.