The primary goal of this study was to develop descriptive image interpretation criteria and a classification of endoscopic ultrasound-confocal microscopy (EUS-CM) findings in pancreatic masses and lymph nodes through a review of prospectively obtained EUS-CM videos from proven malignant and benign cases, and to propose diagnostic criteria for predicting malignancy. The material used was a 19-G EUS-needle in which the stylet was replaced by the confocal mini-probe. The mini-probe pre-loaded in the EUS-needle was guided endosonographically in the target then the mini-probe was pushed under EUS guidance into the lesion. Eleven patients mean age 62.3 years underwent EUS for the staging of a pancreatic mass (3 cystic and 4 solid) or for the diagnosis of celiac and/or mediastinal LN (n = 4). Benign intraductal papillary mucinous neoplasm (IPMN) was characterized by the aspect of finger-like projections which correspond to the villous changes of intestinal IPMN type. In pancreatic adenocarcinomas, EUS-CM found vascular leakage with irregular vessels with leakage of fluorescein into the tumor, large dark clumps which correspond to humps of malignant cells. Inflammatory lymph nodes were characterized by the presence of diffuse small cells into a homogeneous stroma with a normal vascularization. At the opposite, EUS-CM showed in malignant lymph node glandular structures with dark cells, large dark clumps and an important neo-vascularization with huge leakage of fluorescein.