Endoscopic ultrasonography (EUS) is superior to all other imaging modalities in detecting small pancreatic cancers. However, its ability to characterize hypoechoic pancreatic masses is limited: most carcinomas, neuroendocrine tumors, and inflammatory pseudotumors are simply depicted as hypoechoic masses. Contrast enhancement helps EUS to characterize such hypoechoic masses. Intravenous ultrasound (US) agents increase the signal from the blood and, thus, act as amplifiers and improve visualization of blood flow in small vessels using Doppler US. Contrast-enhanced Doppler EUS can differentiate small pancreatic carcinomas that cannot be detected by other imaging modalities. The development of second-generation US contrast agents and an EUS system with a broad-band transducer enabled the visualization of microvessels and the parenchymal perfusion in the pancreas. This contrast-enhanced harmonic EUS has shown that most pancreatic cancers exhibit hypovascular heterogeneous enhancement with irregular network-like microvessels. Moreover, it can diagnose pancreatic cancers with a high sensitivity (89-92%). Copyright (C) 2011 S. Karger AG, Basel and IAP