Once malignant mesothelioma is found, staging will be done to find out if cancer cells have spread to other parts of the body. Staging of mesothelioma is based on imaging studies such as x-rays, CT scans, and MRI scans. Peritoneal mesothelioma is not staged while there are three staging systems for pleural mesothelioma.

The most often used Butchart System is based mainly on the extent of primary tumor mass and divides mesotheliomas into four stages.

Stage I - Mesothelioma is present in the right or left pleura and may also involve the lung, pericardium or diaphragm on the same side.
Stage II - Mesothelioma invades the chest wall or involves the esophagus, heart, or pleura on both sides. Lymph nodes in the chest may also be involved.
Stage III - Mesothelioma has penetrated through the diaphragm into the peritoneum. Lymph nodes beyond those in the chest may also be involved.
Stage IV - There is evidence of metastasis or spread through the bloodstream to other organs.

The recent TNM system is similar to staging systems used for most other cancers.
- Stage I - Mesothelioma involves right or left pleura and may also have spread to the lung, pericardium, or diaphragm on the same side. Lymph nodes are not involved.
- Stage II - Mesothelioma has spread from the pleura on one side to nearby lymph nodes next to the lung on the same side. It may also have spread into the lung, pericardium, or diaphragm on the same side.
- Stage III - Mesothelioma has spread into the chest wall, muscle, ribs, heart, esophagus, or other organs in the chest on the same side as the primary tumor, with or without spread to subcarinal or mediastinal lymph nodes on the same side as the primary tumor. Subcarinal nodes are located at the point where the windpipe branches to the left and right lungs. Mediastinal lymph nodes are located in the space behind the chest bone in front of the heart.
- Stage IV - Mesothelioma has spread into the lymph nodes in the chest on the side opposite the primary tumor, or directly extends to the pleura or lung on the opposite side, or into organs in the abdominal cavity or neck. Any distant metastases is included in this stage.
The latest Brigham System stages mesothelioma according to resectability (the ability to surgically remove) and lymph node involvement
- Stage I - Resectable mesothelioma and no lymph node involvement
- Stage II - Resectable mesothelioma but with lymph node involvement
- Stage III - Unresectable mesothelioma extending into chest wall, heart, or through diaphragm, peritoneum; with or without extrathoracic lymph node involvement
- Stage IV - Distant metastatic disease.