The dismal prognosis of pancreaticobiliary malignancies is mainly attributed to the extremely difficult detection of early-stage lesions, including intraepithelial neoplasia. To improve prognosis, several studies on the early detection of cancer have been conducted using bile and pancreatic juices for pathological or molecular analyses. One approach is liquid biopsy that includes information about the tumor, such as circulating tumor cells, circulating tumor DNA, microRNAs, and exosomes released by the tumor. Another approach is proteomics/metabolomics that reflects specific conditions in the tumor. These two approaches lead to artificial intelligence-based multiomics analyses that comprises genomics, proteomics/metabolomics, and transcriptomics. Based on the findings of molecular analysis, pathological analysis using immunohistochemical staining/fluorescence in situ hybridization has also been developed. Moreover, there have been reports of new methods/ingenuities for obtaining appropriate samples for the diagnosis of early-stage cancer. Here we review the knowledge on cutting-edge pathological and molecular analyses of bile and pancreatic juices, introduce some ingenuities in sampling and sample processing to promote effective clinical practice, and provide a basis for future studies.