Mesothelioma is primarily caused by asbestos exposure. Though the exact way asbestos causes mesothelioma is currently being researched, medical professionals have a number of theories:

- Asbestos causes irritation and inflammation of mesothelial cells, which results in irreversible scarring, cellular damage, and eventually cancer.

- Asbestos fibers enter cells and disrupt the function of cellular structures that are essential for normal cell division, causing cellular changes that lead to cancer.

- Asbestos causes the production of free radicals. These molecules damage DNA, and cause cells to mutate and become cancerous.

- The presence of asbestos causes cells to produce oncoproteins. These molecules cause mesothelial cells to ignore normal cellular division restraints, and this can lead to the development of cancer.