The diagnosis of pancreatic cancer is devastating for patients and their relatives as the incidence rate is approximately the same as mortality rate. Only a small percentage, which ranges from 0.4% to 4% of patients who have been given this diagnosis, will be alive at five years. At the time of diagnosis, 80% of pancreatic cancer patients have unresectable or metastatic disease. Moreover, the therapeutic alternatives offered by chemotherapy or radiotherapy are few, if not zero. For all these reasons, there is an imperative need of analyzing and understanding the primitive lesions that lead to invasive pancreatic adenocarcinoma. Molecular pathology of these lesions 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. This review focuses on medical research on pancreatic cancer models and the underlying genetic alterations. The diagnosis of pancreatic cancer is devastating for patients and their relatives as the incidence rate is approximately the same as mortality rate. Only a small percentage, which ranges from 0.4% to 4% of patients who have been given this diagnosis, will be alive at five years. At the time of diagnosis, 80% of pancreatic cancer patients have unresectable or metastatic disease. Moreover, the therapeutic alternatives offered by chemotherapy or radiotherapy are few, if not zero. For all these reasons, there is an imperative need of analyzing and understanding the primitive lesions that lead to invasive lesions aden thearcinoma. Molecular pathology of these lesions 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. This review focuses on medical research on pancreatic cancer models and the underlying genetic alterations.