There is an urgent need for novel and reliable biomarkers for the diagnosis and prognostication of pancreatic ductal adenocarcinoma (PDAC). Circulating microRNAs (miRNAs) have been extensively profiled in PDAC blood samples, but few studies have performed adequate validation of candidate markers. The evaluated study by Xu et al. investigated pre-operative plasma miRNAs from PDAC patients over three phases and three surgical centers. They revealed miR-486-5p and miR-938 were able to discriminate PDAC patients from healthy controls and those with chronic pancreatitis. The diagnostic ability of miR-486-5p for identifying PDAC from healthy controls was comparable to that of CA 19-9. This study provides further evidence for the use of blood-based miRNAs as diagnostic biomarkers in PDAC. However, as these have not been identified in previous studies these require further validation and methodology needs to be standardized if these are ever to be used in the clinic.