Working with asbestos is the greatest risk element for mesothelioma. In the United States, asbestos is the greatest source of malignant mesothelioma and has been deliberated "indisputably" linked with the development of mesothelioma. Indeed, the bond between asbestos and mesothelioma is so tough that more analyze mesothelioma a “signal” or “sentinel” tumor. A past file of asbestos exposure survives in most cases. However, mesothelioma has been stated in some separate people without any famous exposure to asbestos. In infrequent instances, mesothelioma has in addition been linked with irradiation, intrapleural thorium dioxide (Thorotrast), and inhalation of other fibrous silicates, for instance erionite. Some research put forward that simian virus 40 (SV40) may play-act as a cofactor in the development of mesothelioma.

Asbestos was famous in antiquity, but it was not mined and extensively employed commercially until the late 19th century. Its use highly advanced as long as World War II. Since the early 1940s, millions of American staff has been uncovered to asbestos dust. Initially, the threats linked with asbestos exposure were not publicly known. However, an advanced risk of deducing mesothelioma was afterwards encountered amid shipyard staff, population who work in asbestos mines and mills, makers of asbestos yield, staff in the way of heating and makeup businesses, and other exchanges people. Today, the agent location of the U.S. Occupational Safety and Health Administration (OSHA) and the U.S. EPA is that protections and "permissible exposure limits" demanded by U.S. controls, while enough to stop most asbestos-related non-malignant illness, they are not enough to stop or look after in resistance to asbestos-related cancers for instance mesothelioma. Likewise, the British Government's Health and Safety Executive (HSE) states formally that any threshold for mesothelioma ought be at a very small stage and it is extensively accepted that if any such threshold does survive at all, then it not able to presently be quantified. For useful intents, consequently, HSE presumes that no such "safe" threshold exists. Others have found as well that there is no established items of a threshold stage under which there is no risk of mesothelioma. There becomes noticeable to be a linear, dose-response bond, with advancing dose generating advancing disease. Nevertheless, mesothelioma may be connected to condensed, small stage or rambling exposures to asbestos. The dose needed for issue becomes noticeable to be worse for asbestos-induced mesothelioma than for pulmonary asbestosis or lung cancer. Again, there is no famous secure stage of exposure to asbestos as it links to advanced risk of mesothelioma.

The interval of exposure to asbestos producing mesothelioma can be short. For instance, instances of mesothelioma have been documented with only 1–3 months of exposure. People who work with asbestos wear private defensive apparatus to worse their risk of exposure.