Purpose <p>The diagnostic methods for accurately differentiating the dignity of pancreatic neoplasms are limited. Worrisome features on MRI and endosonography guide the way to resection or conservative treatment with a relevant rate of failure. Intraoperative minimal invasive optical coherence tomography could be a solution for this challenge.&#xa0;The aim of this study is to investigate whether optical coherence tomography is suitable for differentiating of pancreatic neoplastic lesions.</p> Methods <p>In this exploratory study, four patient’s specimens of pancreatic resections (white adipose tissue, intraductal papillary mucinous neoplasm (IPMN), pancreatic ductal adenocarcinoma (PDAC) based on IPMN and neuroendocrine pancreatic carcinoma) were prospectively examined ex vivo immediately after resection in the operating room using an optical coherence tomography system (Callisto 930nm, Thorlabs GmbH). In detail, the study investigated whether and in what way endocrine tumors, adenocarcinomas, premalignant and benign cysts differ morphologically in optical coherence tomography imaging compared to healthy pancreatic tissue. The final histopathological findings of the pancreatic specimens served as a reference and were correlated.</p> Results <p>The samples examined ranged from typical fatty tissue, intraductal papillary mucinous neoplasm (IPMN), a moderate differentiated (G2) pancreatic ductal adenocarcinoma (PDAC) based on an intraductal papillary mucinous neoplasm (IPMN) and a neuroendocrine pancreatic carcinoma. Optical coherence tomography was feasible to replicate key histological characteristics and tissue architecture in correlation to conventional Hematoxylin-eosin histology.</p> Conclusion <p>Optical coherence tomography imaging has the potential to differentiate between benign, pre-malignant and malignant pancreatic pathologies by morphology and should be examined in larger collectives.</p>