We report the first case of a posterior mediastinal granular cell tumor initially diagnosed on cytologic material obtained via endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in a 51-year-old male with a prior history of colon cancer. Aspirates obtained were cellular and composed of polygonal cells with abundant granular cytoplasm and small, round dark nuclei. An immunoperoxidase stain performed on the cell block for antibodies to S-100 protein showed strong, diffuse staining of the cytoplasmic granules. Electron microscopy performed on the cell block revealed numerous cytoplasmic lysosomes. This is the first case report in the English literature of a definitive preoperative diagnosis of a mediastinal granular cell tumor utilizing material obtained via EUS-FNA. © 2005 Bean et al; licensee BioMed Central Ltd.