In the last decade, intraductal papillary mucinous neoplasms (IPMNs) have become commonly diagnosed. From a morphological standpoint, they are classified in main-duct IPMNs (MD-IPMNs) and branch-duct IPMNs (BD-IPMNs), depending on the type of involvement of the pancreatic ductal system by the neoplasm. Despite the fact that our understanding of their natural history is still incomplete, recent data indicate that MD-IPMNs and BD-IPMNs show significant differences in terms of biological behaviour with MD-IPMNs at higher risk of malignant degeneration. In the present paper, clinical and epidemiological characteristics, rates of malignancy and the natural history of MD-IPMNs and BD-IPMNs are analyzed. The profile of IPMNs involving both the main pancreatic duct and its side branches (combined-IPMNs) are also discussed. Finally, general recommendations for management based on these differences are given.