Asbestos exposure is the main cause of mesothelioma. After these fibers are breathed in, they travel to the ends of small air passages and reach the pleura where they damage mesothelial cells. The damage they cause is through inflammation and scarring as well as stimulating the growth of these cells. Finally, they may damage DNA and cause changes that result in uncontrolled growth. In addition, they also cause injury to lung cells that can result in lung cancer and/or asbestosis (replacement of lung tissue by scar tissue). If swallowed, these fibers can reach the abdominal cavity where they have a role in causing peritoneal mesothelioma.

Researchers are studying exactly how asbestos causes mesothelial cells to develop into mesothelioma. It is still not known whether the SV40 virus participates in this process.