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Early diagnosis of pancreatic cancer, particularly in intraductal papillary mucinous neoplasm (IPMN), remains challenging despite advances in imaging and biomarkers. Pancreatic adenocarcinoma has a high mortality rate, therefore its early detection and adequate interventions are necessary to improve the disease outcome. Most IPMNs are asymptomatic and discovered incidentally. MRI is a preferred tool for diagnosing malignant IPMN, with sensitivity 90.7–94.1% and specificity 84.7–87.2% in detecting mural nodules >5 mm, a strong predictor of high-risk lesions. Radiomics further enhances diagnostic accuracy (sensitivity 91–96%, specificity 78–81%), especially when combined with CA 19-9, which has lower sensitivity (73–90%) but higher specificity (79–95%). CT, though less effective for small mural nodules, remains widely used; its accuracy improves with radiomics and clinical variables (sensitivity 90.4%, specificity 74%). Conventional EUS shows lower performance (sensitivity 60%, specificity 80%), but its advanced variations have improved outcomes. Contrast-enhanced EUS visualizes mural nodules with more than 90% sensitivity and involvement of main pancreatic duct with sensitivity 83.5% and specificity 87%. EUS-fine needle aspiration allows cyst fluid analysis; however, CEA, glucose, and KRAS/GNAS mutations show poor value for malignancy risk. Cytology has low sensitivity (28.7–64.8%) but high specificity (84–94%) in diagnostic malignant changes and strongly affects further management. EUS-through the needle biopsy yields high diagnostic accuracy (sensitivity 90%, specificity 95%) but carries a range 2–23% adverse events, which limits its wide use. EUS-confocal laser endomicroscopy provides real-time microscopic evaluation, detecting malignant IPMN with sensitivity 90% and specificity 73%, though its availability is limited. New emerging biomarkers available in cyst fluid or blood include mucins, miRNA panels (sensitivity 66.7–89%, specificity 89.7–100%), lipidomics, and cancer metabolite profiling, with diagnostic accuracy approaching 89–91%. Pancreatoscopy enables direct MPD visualization and biopsy with sensitivity 64–100% and specificity 75–100%, though adverse events occur in around 12% cases. Combining advanced imaging, EUS-based tissue acquisition, and novel biomarkers holds promise for earlier and more accurate detection of malignant IPMN, potentially improving PDAC outcomes.