Malignant pleura mesothelioma (MPM) is a rare aggressive cancer arising from serous surfaces due to asbestos inhalation. Pleura is the most common site (65%-70%), followed by peritoneum (30%), tunica vaginalis and pericardium (1%-2%). MPM is more common in men than in women (5:1) due to occupational exposure. The median age ranges vary from 45 to 85 years. Mesothelioma global incidence as compared with other cancers is less than 1%. The World Health Organization (WHO) recently estimated that ∼107,000 people in the world die each year from asbestos-related diseases. MPM is classified into 3 major sub-types based on histological basis: Epithelioid, sarcomatoid and mixed or biphasic. The epithelioid tumors are most common type representing 50% to 70% of all MPM diagnosed. It is less aggressive and responds to the treatment better. Diagnostic procedures can be either non-invasive such as Chest X-ray, CT, FDG-PET or invasive such as image-guided (CT or US) pleural biopsy or laparoscopy. Video-assisted thoracoscopy is the best biopsy and cytology technique (accuracy of 98%), a reliable diagnostic tool for experienced cytopathologists, can offer additional tissue confirmation.