Malignant mesothelioma is a rare neoplasm. It has been noted in the literature that fine needle aspiration (FNA) is a useful tool for the diagnosis of mesothelioma. However, the differential diagnosis may require use of a battery of immunohistochemical stains. Clinico-radiologic correlation is also crucial. Real time endoscopic ultrasound (EUS) combined with FNA has been shown to be a very sensitive technique to obtain samples from different organ sites, including mediastinal lesions. The use of EUS-FNA for the diagnosis of mesothelioma, reinforces the role of a cytopathologist as a cohesive team player along with a radiologist and a clinician during on-site assessment for the proper triage of additional specimens for ancillary studies leading to a better patient management.