Pancreatic neoplasms represent a broad range of clinical entities, many of which have drastic effects on the lives of patients. Recently, high-throughput sequencing analyses have been performed in many pancreatic neoplasms, providing deep insights into the underlying biology of these neoplasms as well as novel approaches to diagnosis and treatment. This review discusses the molecular alterations underlying pancreatic neoplasms as well as the clinical impact of these alterations for diagnosis and treatment.