The earlier symptoms of malignant pleural mesothelioma are very similar to those experienced with other lung conditions, such as pneumonia or lung cancer. Symptoms also tend to present very gradually, and may therefore go unnoticed for a while. Breathlessness is one of the early and more common symptoms of pleural mesothelioma. This may present as a recent onset of shortness of breath, or a recent increase in shortness of breath. Breathlessness may be caused by a buildup of fluid (pleural effusion) in the space surrounding the lungs. This buildup of fluid may be removed periodically to make breathing easier. Certain substances may also be introduced into the space between the pleural membranes where fluid collects. These substances cause an inflammatory reaction in the pleural membranes, causing them to fuse together and thereby preventing the formation and collection of more fluid.

The thickening of the pleural membranes due to the growth of cancer cells also restricts lung function and contributes to breathlessness. Sometimes, this thickened tissue may require surgical removal to restore some lung function. The removal process is called decortication or pleurectomy.

Malignant mesotheliomas tend to spread fairly rapidly to other parts of the body, and this spread can result in additional symptoms. When pleural mesothelioma spreads to the chest wall and other tissues in the chest, it can result in severe pain. Even before the cancer spreads, chest pain, particularly in the lower chest and side, may be experienced. Chest pain tends to become progressively worse as the cancer spreads. Severe pain may be treated with strong pain-relieving drugs or with radiotherapy. When pleural mesothelioma spreads to the lungs, symptoms that are typically seen in lung cancer, such as hoarseness and coughing up of blood, may be present.

As with other cancers, the effect of pleural mesothelioma is widespread. The increased metabolism caused by cancer cells results in fever, weight loss and fatigue.