Conventional endoscopic ultrasonography (EUS) has limitations in the diagnosis of solid masses. Because most are depicted as a hypoechoic mass, without cytology or biopsy, it can be difficult to distinguish inflammatory masses from malignancy. Recently developed, contrast-enhanced harmonic EUS (CH-EUS) has improved characterization of digestive lesions by depicting microvessels and parenchymal perfusion, particularly for differentiating pancreatic cancer from other pancreatic solid lesions, identifying mural nodules in intraductal papillary mucinous neoplasms, and estimating malignant potential of gastrointestinal stromal tumors. CH-EUS is complementary to EUS-guided fine-needle aspiration for diagnosing pancreatic lesions, staging, and predicting chemotherapy response.