Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by early invasiveness and resistance to treatment. Surgery in early stages is the only effective treatment, thus finding new biomarkers for the early detection of PDAC remains a major challenge. The present study aimed to compare the immunoproteome between PDAC patients and healthy controls using serological proteome analysis method. Firstly, cell lysates from two different pancreatic cancer cell lines were separated by two dimensional (2D) gels, and then transferred onto membranes probed with sera from 20 PDAC patients and 10 healthy controls. Proteins differentially reacting with autoantibodies in PDAC patients and control groups and were identified using mass spectrometry. This process led to the identification of 18 pancreatic immunoreactive antigens such as laminin, superoxide dismutase, ATP synthase, Rho GDP-dissociation inhibitor II, septin, glyceraldehyde 3-phosphate-dehydrogenase, phosphoglycerate mutase B, tubulin β8 channel and prohibit in. In the present study, we identified 18 immunoreactive proteins in PDAC. While the identified proteins were critically involved in PDAC pathogenesis, further investigation in a large scale population will determine the applicability of these potential biomarkers for the early diagnosis or treatment of the disease.