Background/Aims: High-grade pancreatic intraepithelial neoplasia and invasive pancreatic duc-tal adenocarcinoma ≤10 mm are targets for early detection of pancreatic cancer. However, their imaging characteristics are unknown. We aimed to identify endoscopic ultrasound findings for the detection of these lesions. Methods: Patients diagnosed with high-grade pancreatic intraepithelial neoplasia (n=29), pan-creatic ductal adenocarcinoma ≤10 mm (n=11) (who underwent surgical resection), or benignmain pancreatic duct stenosis (n=20) between January 2014 and January 2021 were retrospectively included. Six features differentiating these lesions were examined by endoscopic ultraso-nography: main pancreatic duct stenosis, upstream main pancreatic duct dilation, hypoechoic areas surrounding the main pancreatic duct irregularities (mottled areas without demarcation or round areas with demarcation), branch duct dilation, prominent lobular segmentation, and atrophy. Interobserver agreement was assessed by two independent observers. Results: Hypoechoic areas surrounding the main pancreatic duct irregularities were observedmore frequently in high-grade pancreatic intraepithelial neoplasia (82.8%) and pancreatic ductal adenocarcinoma ≤10 mm (90.9%) than in benign stenosis (15.0%) (p<0.001). High-grade pan-creatic intraepithelial neoplasia exhibited mottled hypoechoic areas more frequently (79.3% vs 18.9%, p<0.001), and round hypoechoic areas less frequently (3.4% vs 72.7%, p<0.001), than pancreatic ductal adenocarcinoma ≤10 mm. The sensitivity and specificity of hypoechoic areas for differentiating high-grade pancreatic intraepithelial neoplasia, pancreatic ductal adenocarci-noma ≤10 mm, and benign stenosis were both 85.0%, with moderate interobserver agreement. Conclusions The hypoechoic areas surrounding main pancreatic duct irregularities on endo-scopic ultrasound may differentiate between high-grade pancreatic intraepithelial neoplasia, pan-creatic ductal adenocarcinoma ≤10 mm, and benign stenosis (Trial Registration: UMIN Clinical Trials Registry (UMIN000044789).