Pancreatic cancer is one of the most lethal of all the solid malignancies. Less than 5% of patients in whom pancreatic cancer is diagnosed today will be alive in 5 years. (1) Few therapies are effective, and until recently, painfully little was known about this disease. Today, a number of advances have made pancreatic pathology an exciting and rapidly advancing field. First, it is now clear that pancreatic cancer aggregates in some families, and some of the genes responsible for the familial aggregation of pancreatic cancer have been discovered. (2,3) Second, a number of precursor lesions, such as pancreatic intraepithelial neoplasia, which can give rise to invasive pancreatic cancer, have been described and are now well characterized. (4,5) Third, preliminary attempts to detect pancreatic neoplasia early in asymptomatic individuals show promise of success. (6,7) Fourth, a number of variants of pancreatic cancer with differing genetic and clinical features have been described. (8-10) Fifth, we have a much better understanding of the subtypes and natural biology of cystic lesions of the pancreas, including intraductal papillary mucinous neoplasm and mucinous cystic neoplasm. (11-13) These cystic neoplasms are important because they represent a real opportunity to cure pancreatic neoplasia before an invasive cancer develops. (14-16) Finally, there has been a revolution in our understanding of the genetic changes and gene expression patterns that characterize pancreatic cancer. (17-19) The time is ripe to apply these advances to improve patient care. In this special issue of the ARCHIVES, an international panel of experts presents a comprehensive review of the most important pancreatic diseases that pathologists are likely to encounter in their practices. The full spectrum of these diseases is discussed--from modern molecular understandings to easy-to-follow algorithms for clinical diagnoses. This issue leads off with a comprehensive review of endocrine neoplasms of the pancreas by Capelli et al. They deftly integrate modern molecular biology with a description of up-to-date diagnostic and prognostic indicators, and thereby bring the reader to a deeper understanding of these less aggressive, but nonetheless malignant neoplasms of the pancreas. Next, Dr Klein and colleagues review familial pancreatic cancer. They define the clinical syndromes associated with an increased risk of pancreatic cancer and show how family history of cancer can be used to predict a patient's risk of developing pancreatic cancer. Dr Offerhaus and colleagues then comprehensively describe pancreatic intraepithelial neoplasia, the earliest precursors to invasive pancreatic cancer. They illustrate the histologic and genetic progression from normal tissue to precursor to invasive cancer in both humans and mouse models. An understanding of these precursors is obviously critically important to early detection efforts. (20) Drs Kloppel and Adsay then discuss the next step in the progression of pancreatic cancer and review the differential diagnosis in pancreas pathology--invasive pancreatic cancer versus chronic pancreatitis. The distinction between these two entities is not only critically important for the patient, but, in our experience, is also one of the most difficult in surgical pathology. The guidelines presented by Kloppel and Adsay are therefore critically important. Cytology is growing in importance, and Drs Stelow and Bellizzi next present an extremely user-friendly algorithmic approach to the evaluation of cytologic specimens from the pancreas.