This is a state-of-the-art review of the molecular genetics of pancreatic neoplasms. Although understanding of the molecular features underlying pancreatic neoplasms is still in its infancy, a strong emphasis on the relevance of these findings for the practicing surgical pathologist is provided. The application of molecular techniques has yielded a wealth of information that may soon enhance diagnostics, and will also lead to the development of safer, more effective targeted therapies. The pathologist will play a key role in integrating the current pathologic classification system with newly validated molecular markers.