Most pancreatic cancer patients present with advanced metastatic disease, resulting in extremely poor 5-year survival, mainly because of the lack of a reliable modality for early detection and limited therapeutic options for advanced disease. Therefore, there is a need for minimally-invasive diagnostic tools for detecting pancreatic cancer at an early stage, when curative surgery and also novel therapeutic approaches including precision medicine may be feasible. The 'liquid biopsy' addresses these unmet clinical needs based on the concept that simple peripheral blood sampling and detection of circulating tumor DNA(ct DNA) could provide diagnostic information. In this review, we provide an overview of the current status of bloodbased tests for diagnosis of pancreatic cancer and the potential utility of ct DNA for precision medicine. We also discuss challenges that remain to be addressed in developing practical ct DNA-based liquid biopsy approaches for early diagnosis of pancreatic cancer.