Diagnosing mesothelioma is often difficult, because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient's medical history, including any history of asbestos exposure. A complete physical examination may be performed, including x-rays of the chest or abdomen and lung function tests. A CT (or CAT) scan or an MRI may also be useful. A CT scan is a series of detailed pictures of areas inside the body created by a computer linked to an x-ray machine. In an MRI, a powerful magnet linked to a computer is used to make detailed pictures of areas inside the body. These pictures are viewed on a monitor and can also be printed.

A biopsy is needed to confirm a diagnosis of mesothelioma. In a biopsy, a surgeon or a medical oncologist (a doctor who specializes in diagnosing and treating cancer) removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples. If the cancer is in the abdomen, the doctor may perform a peritoneoscopy. To obtain tissue for examination, the doctor makes a small opening in the abdomen and inserts a special instrument called a peritoneoscope into the abdominal cavity. If these procedures do not yield enough tissue, more extensive diagnostic surgery may be necessary.

If the diagnosis is mesothelioma, the doctor will want to learn the stage (or extent) of the disease. Staging involves more tests in a careful attempt to find out whether the cancer has spread and, if so, to which parts of the body. Knowing the stage of the disease helps the doctor plan treatment.

Mesothelioma is described as localized if the cancer is found only on the membrane surface where it originated. It is classified as advanced if it has spread beyond the original membrane surface to other parts of the body, such as the lymph nodes, lungs, chest wall, or abdominal organs.