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Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has proven itself to be a reliable method for the diagnosis of gastrointestinal stromal tumors and other gastrointestinal mesenchymal neoplasms. The diagnosis and distinction of these entities remain important, as these neoplasms have different prognoses and treatment options. We present a case of a 14.5-cm esophageal mass in a 67-yr-old woman sampled by EUS-FNA. Smears showed a cellular, spindle cell lesion with marked cytologic and nuclear pleomorphism. A cell block showed neoplastic cells reacting strongly with antibodies to smooth muscle antigens and not with antibodies to keratin, CD34 and CD117. Resection confirmed the diagnosis of esophageal leiomyosarcoma. To the best of our knowledge, this represents the first reported case of an esophageal leiomyosarcoma diagnosed by EUS-FNA. Clinical, imaging, and cytologic features as well as differential diagnosis are discussed.