Pancreatic cystic and neoplasms are being diagnosed with increasing frequency. Accurate diagnosis and determination of benign versus malignant lesions is crucial for determining need for surveillance versus surgery or endoscopic therapy as well as avoiding unnecessary surgery in cysts with no malignant potential. Tumor markers such as KRAS and GNAS hold promise, but which molecular marker or a combination of markers is most useful and cost effective remains to be seen. Advanced imaging with confocal laser endomicroscopy can serve as an optical biopsy and play a part in the diagnostic algorithm. Microforceps aided biopsy of pancreatic cyst wall and tumor contents hold great promise as they allow direct tissue acquisition. Much progress has been made in the role of EUS guided evaluation of pancreatic cystic neoplasms over the last several years, and with the advances enumerated above, the future is more than just a few shades of grey. Future studies should include prospective multiarm trials of microforceps biopsy versus conventional EUS-FNA and use of biochemical and molecular markers, confocal laser endomicroscopy or a combination thereof to determine best approach to pancreatic cystic neoplasms. In Osler’s words, ‘Medicine is a science of uncertainty and an art of probability’. Incorporation of advanced imaging and molecular markers into a new diagnostic algorithm with subsequent validation through retrospective and prospective studies has the potential to increase diagnostic accuracy and guide optimal management of patients and improve outcomes. Accurate diagnosis and determination of benign versus malignant lesions is crucial for determining need for surveillance versus surgery or endoscopic therapy as well as avoiding unnecessary surgery in cysts with no malignant potential. Tumor markers such as KRAS and GNAS hold promise, but which molecular marker or a combination of markers is most useful and cost effective remains to be seen. Advanced imaging with confocal laser endomicroscopy can serve as an optical biopsy and play a part in the diagnostic algorithm. Microforceps aided biopsy of pancreatic cyst wall and tumor contents hold great promise as they allow direct tissue acquisition. Much progress has been made in the role of EUS guided evaluation of pancreatic cystic neoplasms over the last several years, and with the advances enumerated above, the future is more than just a few shades of gray. Future studies should include prospective multiarm tr In Osler’s words, ’Medicine is a science of uncertainty and an art of probability’ Incorporation of advanced imaging and molecular markers into a new diagnostic algorithm with subsequent validation through retrospective and prospective studies has the potential to increase diagnostic accuracy and guide optimal management of patients and improve outcomes.