OBJECTIVES: Among subepithelial lesions (SELs), gastrointestinal stromal tumors (GISTs) should be identified and surgically treated at an early stage. However, it is difficult to diagnose SELs smaller than 20 mm. In recent years, endoscopic ultrasound (EUS) elastography (EUS-EG) and contrast-enhanced harmonic EUS (CH-EUS) have been reported to be useful for the diagnosis of SELs, although the diagnostic accuracy of a combination of EUS techniques with image enhancement is unknown. METHODS: Patients with SELs who underwent EUS-guided tissue acquisition, EUS shear-wave elastography (EUS-SWE), EUS strain elastography (EUS-SE), and CH-EUS from January 2019 to June 2023 were enrolled. To assess the diagnostic accuracy for differentiating GISTs from other SELs, shear-wave velocity on EUS-SWE, the strain ratio on EUS-SE, and vascularity on CH-EUS were determined and their diagnostic accuracies were compared. RESULTS: Forty-three patients were enrolled. When the cut-off value was set at 3.27 m/s, the sensitivity, specificity, and diagnostic accuracy of shear-wave velocity were 28.6%, 86.2%, and 34.9%, respectively. When the cut-off value was set at 3.79, the sensitivity, specificity, and diagnostic accuracy of the strain ratio were 93.1%, 64.3%, and 83.7%, respectively. The sensitivity, specificity, and diagnostic accuracy of CH-EUS were 79.3%, 92.3%, and 83.7%, respectively. When EUS-SE was combined with CH-EUS, the sensitivity and diagnostic accuracy were the highest among binary combinations of image enhancement modalities. CONCLUSIONS: EUS-SE and CH-EUS are useful for differentiating GISTs from other SELs. Furthermore, the use of both modalities may further improve the identification of GISTs.