Pancreatic cancer represents a major challenge for research studies and clinical management. No specific tumor marker for the diagnosis of pancreatic cancer exists. Therefore, extensive genomic, transcriptomic, and proteomic studies are being developed to identify candidate markers for use in high-throughput systems capable of large cohort screening. Understandably, the complex pathophysiology of pancreatic cancer requires sensitive and specific biomarkers that can improve both early diagnosis and therapeutic monitoring. The lack of a single diagnostic marker makes it likely that only a panel of biomarkers is capable of providing the appropriate combination of high sensitivity and specificity. Biomarker discovery using novel technology can improve prognostic upgrading and pinpoint new molecular targets for innovative therapy.