People often talk about mesothelioma and lung cancer together because both affect the chest and can cause similar symptoms, but they are actually two very different diseases. Understanding the differences is crucial, especially for people with a history of asbestos exposure who might be considering legal action. What is the Main Difference? The biggest difference is in where each cancer starts. Mesothelioma forms in the mesothelium, the thin layer that wraps around organs like the lungs, abdomen, and heart.