The only known cause of pleural mesothelioma is exposure to asbestos fibers, which are inhaled into the lungs and become lodged there. From the lung, asbestos fibers are thought to move to the pleura in a few different ways: first, by translocution (in which the fibers actually move through lung tissue to the outside of the lung and are picked up buy the pleura); second, by clearance through the lymphatic system, and third, through the blood stream.

Usually it takes at least 20 years from the time a person is exposed to asbestos until they develop mesothelioma. This is called the latency period. Sometimes the disease does not occur for 40, 50 or even 60 years after the person is exposed to asbestos. This explains the fact that the vast majority of persons diagnosed with mesothelioma are seniors. Rarely, the disease can occur in people in their 30's and 40's.