This report describes the case of a man who underwent subtotal esophagectomy for the concomitant presence of a multifocal esophageal squamous carcinoma and a granular cell tumor (GCT); he had been previously affected by another metachronous esophageal GCT excised endoscopically. This is the sixth case described in the literature detailing other cases of a combination of malignancies involving additional organs. We emphasize the need for a prolonged surveillance of patients with multiple GCTs in order to promptly recognize the possibility of associated neoplasms.