Endoscopic ultrasonography (EUS) plays a major role in diagnosing gallbladder (GB) cancer and pancreatic cancer (PC). In cases of GB cancer, EUS allows for precise observations of morphology and wall layers. However, proficiency is required for the morphologic diagnosis of GB tumors. Therefore, contrast-enhanced harmonic EUS (CH-EUS) began to be performed to diagnose GB lesions. CH-EUS enables real-time observation of the hemodynamics of GB tumors. The enhanced patterns generated by CH-EUS improve precision in the diagnosis of such tumors.PC appears as a hypoechoic mass on EUS. However, distinguishing between PC and mass-forming pancreatitis or focal autoimmune pancreatitis (AIP) is difficult via conventional EUS. CH-EUS allows for differentiating among these diseases (PC is hypoenhanced and heterogeneously enhanced, pancreatitis is isoenhanced, and a pancreatic neuroendocrine tumor is hyperenhanced). EUS-guided fine needle aspiration (EUS-FNA) also contributes to pathological diagnoses of pancreatic lesions. However, certain PC patients cannot be diagnosed via EUS-FNA. PC is heterogeneously enhanced on CH-EUS, and unenhanced regions have been reported to be areas of fibrosis or necrosis. CH-EUS-guided fine needle aspiration (CH-EUS-FNA) permits puncturing of the enhanced area while avoiding necrotic and fibrotic regions. Moreover, as CH-EUS findings have been quantitatively analyzed, a time-intensity curve (TIC) has become usable for diagnosing solid pancreatic lesions. CH-EUS-related techniques have been developed and increasingly utilized in the pancreaticobiliary area.