Aim The aim of this study was to reveal better immunohistochemical diagnostic markers for differentiating solid pseudopapillary neoplasm (SPN) from neuroendocrine tumor (NET) and pancreatic ductal adenocarcinoma (PDAC) and examine their prognostic significance in pancreatic tumors. Patients andmethods Wereviewed55pancreaticsurgical specimens of SPN (10 cases), NET (15 cases), and PDAC (30 cases). We carried out comprehensive immunohistochemical profiling using three markers: CD99, E-cadherin, and claudin-5. Results In SPN, 90% (9/10) of the cases displayed paranuclear dot-like immunoreactivity for CD99; in contrast, 100% (15/15) of the cases of pancreatic NETdisplayed membranous staining, and 96.7% (29/30) of PDAC showed no expression of it (P