A poor PDAC prognosis is due to a lack of effective treatment and late diagnosis. The early detection of PDAC could significantly decrease mortality and save lives. Idealbiomarkers for PDAC should be cost-effective, detectable in easily accessible biological material, and present in sufficient concentration in the earliest possible phase of the disease. This review addresses newly selected, simple protein biomarkers—new ones such as thrombospondin-2, insulin-linked binding protein 2, lysophosphatidic acid, and autotaxin and conventional ones such as Ca19-9, inflammatory factors, and coagulation factors. Their possible use in the early detection of PDAC, differentiation from benign diseases, prognosis, and treatment response prediction is discussed. We also address the usefulness of possible combinations of biomarkers in diagnostic panels.