PanNETs are quite distinct from the usual form of pancreatic cancer, the majority of which are adenocarcinomas, which arise in the exocrine pancreas.

The high-grade subtype termed neuroendocrine cancer (NEC) in the WHO scheme, is synonymous with "islet cell carcinoma".

[10]: 43–44  Symptoms such as abdominal or back pain or pressure, diarrhea, indigestion, or yellowing of the skin and whites of the eyes can arise from the effects of a larger PanNET tumor, either locally or at a metastasis.

Up to 90% [12] of PanNETs are nonsecretory or nonfunctional, in which there is no secretion, or the quantity or type of products, such as pancreatic polypeptide (PPoma), chromogranin A, and neurotensin, do not cause a clinical syndrome although blood levels may be elevated.

[18] Measurement of hormones including pancreatic polypeptide, gastrin, proinsulin, insulin, glucagon, and vasoactive intestinal peptide can determine if a tumor is causing hypersecretion.

However, morphological imaging alone is not sufficient for a definite diagnosis[18][20] On biopsy, immunohistochemistry is generally positive for chromogranin and synaptophysin.

[10]: 30 Several targeted therapy agents have been approved in PanNETs by the FDA based on improved progression-free survival (PFS): Pancreatic neuroendocrine tumors may arise in the context of multiple endocrine neoplasia type 1, Von Hippel–Lindau disease, neurofibromatosis type 1 (NF-1) or tuberose sclerosis (TSC)[31][32] Analysis of somatic DNA mutations in well-differentiated pancreatic neuroendocrine tumors identified four important findings:[33][7]