Pancreatic cancer continues to be a deadly malignancy with still high mortality and poor survival. Little progress has been made on the treatment of advanced pancreatic cancer despite the significant advances in understanding,diagnosis,and access to conventional and novel treatments.Molecular pathology of the lesion is the key of our understanding of the mechanisms underlying the development of this cancer and will probably help us in earlier diagnosis and better therapeutic results.New treatment strategies and a more careful evaluation of innovative therapies are clearly needed for this disease.In view of many findings pancreatic cancer should be regarded as a systemic disease,and over the last several years, investigators have gained a better understanding of the molecular biology and events that lead to the development of malignancies.We here review the novel developments in the systemic exploring for commonly mutated genes in pancreatic cancer. Little progress has been made on the treatment of advanced pancreatic cancer despite the significant advances in understanding, diagnosis, and access to conventional and novel treatments. Molecular pathology of the lesion is the key of our understanding of the mechanisms underlying the development of this cancer and will probably help us in earlier diagnosis and better therapeutic results. New treatment strategies and a more careful evaluation of innovative therapies are clearly needed for this disease. view of many findings pancreatic cancer should be regarded as a systemic disease, and over the last several years, investigators have gained a better understanding of the molecular biology and events that lead to the development of malignancies.We here review the novel developments in the systemic exploring for commonly mutated genes in pancreatic cancer.