Subepithelial esophageal tumors (SET) are normally benign intramural esophageal lesions of mesenchymal origin. Although rare, the incidence of SET has increased in recent decades due to the more widespread use of endoscopy and diagnostic imaging. The current review aims to provide an overview of the histopathologic spectrum and the most frequent entities including leiomyoma and gastrointestinal stromal tumor (GIST), diagnostic workup, and multidisciplinary treatment options. Staging for SET should include endoscopy, endoscopic ultrasonography (EUS), and tissue sampling. Current consensus guidelines recommend that SET suggestive of gastrointestinal stromal tumor (GIST) larger than 20���mm or lesions with high-risk stigmata should undergo tissue sampling. Most SET have an excellent long-term outcome, but malignancy may be present in certain subtypes. Asymptomatic SET without high-risk stigmata discovered incidentally usually do not require specific treatment. However, depending on the size and location of the lesion symptoms may occur. Therapeutic interventions range from endoscopic interventional resections to major surgical procedures. Enucleation via minimally invasive or robotic-assisted access remains the standard of care for most SET sub-entities.
