Abstract: Now it has been confirmed that genetic studies are contribute to illuminate the key genes and molecular pathways which promote the formation and progression of pancreatic cancer. Early studies found that the activation of KRAS and the inactivation of CDKN2A, TP53 and SMAD4 occurred with the increased organization atypia degree in the progress of pancreatic intraepithelial neoplasia (PanINs); moreover, these gene mutations led to various important cellular processes and altered signal transduction pathways. Similarly, some relative genes vary in the progress of intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs). Most recently, whole exome sequencing technologies have revealed the genetic landscape of pancreas cancer that arises from preinvasive neoplasms. Such surveys are helpful for the development of new and personalized approaches to clinical management and therapy for pancreatic cancer patients. This review summarizes three kinds of morphological changes of precancerous lesions, respective gene mutation, the relationship between the integrant signaling pathways and regulatory processes and gene mutations in pancreatic cancer precursor lesions.