Pancreatic cancer is the fourth leading cause of cancer related death in the United States. Despite numerous efforts in developing new therapies, the prognosis for patients with pancreatic cancer remains poor. Mouse models for spontaneous pancreatic cancer represent an ideal system to develop immunotherapeutic approaches. The aim of this study was to identify new tumour antigens in a murine model that mimics human disease closely, and to verify the results in patients with pancreatic cancer. We analysed a murine pancreatic complementary DNA expression library with serum from tumour-bearing mice, which led to the identification and isolation of several antigens. One of the antigens repeatedly identified in this screening was Tankyrase-2. Here, we show Tankyrase-2 as an antigen eliciting humoral responses not only in mice with established tumours, but also in mice with pre-malignant lesions. Finally, antibody responses to Tankyrase-2 were found in the serum of patients with pancreatic cancer. Reverse transcriptase-polymerase chain reaction analysis showed Tankyrase-2 expression in human pancreatic tumour. These findings show the relevance of spontaneous murine tumour models for the identification of human tumour antigens.