True leiomyomas of the gastrointestinal system are rare but remain the most common mesenchymal tumors of the esophagus. It has become important to distinguish these tumors from gastrointestinal stromal tumors (GISTs) because the neoplasms have different prognoses and treatment options. We describe and compare clinical findings and the following fine-needle aspiration (FNA) features of 9 gastrointestinal leiomyomas and 19 GISTs sampled with endoscopic ultrasound: overall cellularity, cell group features, cell shape and cytoplasmic features, nuclear characteristics, background, cell block features, and immunohistochemical results. Gastrointestinal leiomyomas and GISTs have different clinical and cytologic features that help pathologists distinguish these tumors, and the immunohistochemical findings that help define these lesions can be derived readily from cell block material obtained by endoscopic ultrasound-guided FNA.