Abstract: The pancreatic neuroendocrine neoplasms presenting significant heterogeneity of characteristics and pro-gnoses is a major clinical challenge. In this review, the data focusing the dilemmas in the diagnosis and treatment of pan creatic neuroendocrine neoplasms are reviewed, such as therapeutic indications, therapeutic sequence and strategy, genetic abnormalities, biomarkers, tumor heterogeneity and classification limitations, and the incorporation of novel diagnosis and therapies into clinical pathway is further discussed.