Clinical relevance of cystic pancreatic lesions has increased over the last years due to a higher detection rate, mainly in asymptomatic subjects, as well as to a better understanding of their natural history. Cystic pancreatic lesions may be benign or malignant. Pancreatic pseudocyst and serous cystadenoma are the most relevant benign cystic lesions of the pancreas. On the other side, mucinous cystadenoma and intraductal pancreatic mucinous neoplasia (IPMN) are the most frequent lesions with a malignant potential. The present article reviews the key aspects for the differential diagnosis of the different cystic pancreatic lesions in clinical practice.