Diagnosing mesothelioma cancer is not easy, as many doctors are still unfamiliar with the symptoms because they are mistaken for a number of common diseases with similar symptoms. To diagnose mesothelioma is difficult because of the latency between contraction and symptoms showing up. When it is diagnosed, mesothelioma cancer is usually in its advanced stages, and little can be done for the patient.

A diagnosis of mesothelioma cancer is obtained with assessment of clinical and radiological findings in addition to a tissue biopsy. A review of the patient's medical history, including history of asbestos exposure is taken. Along with the history, a complete physical examination, x-rays, and lung function tests is given. To support evidence of mesothelioma cancer, a CT scan or MRI may also be given. If any one of these tests provide evidences of mesothelioma cancer, then a biopsy will be necessary to confirm the diagnosis.

If collection of fluids is present in the lungs or around the heart, then a procedure involving thin needle will be used to collect a small example of the fluid for examination. This procedure is called "fine-needle aspiration" may also be used to remove the collection of fluid to relieve symptoms.