Abstract: Disclosed herein are methods for identifying patients likely to have pancreatic ductal adenocarcinoma (PDAC) and patients likely to be at risk for developing PDAC. Related methods are also provided that pertain to patient monitoring, treatment evaluation, and an improved multi-cancer test., as are kits that are suitable for carrying out the aforementioned methods. The invention makes use of hydroxymethylation biomarkers, which in combination with one or more clinical parameters and optionally one or more additional types of biomarkers and/or patient-specific risk factors, exhibit a hydroxymethylation level that correlates with the presence of or risk of developing PDAC.