A 61-year-old man was referred to our hospital for further management of a cystic lesion in the pancreatic head. Contrast-enhanced computed tomography showed a 2-cm cystic lesion with enhancement effects on the cyst wall and a 4-mm hypervascular nodule (Fig. 1A, B). EUS revealed an anechoic cyst with a 4-mm nodule on the cyst wall, which showed early enhancement with Sonazoid contrast (GE Healthcare) (Fig. 1C). Considering its hypervascular nature, we suspected a cystic PNEN. However, the differential diagnoses included IPMN with mural nodules, pancreatic pseudocysts, and cystic degeneration of other solid tumors. Therefore, EUS-TTNB was performed to identify the lesion. The pancreatic cyst was punctured using a 19-gauge EUS-FNA needle (EZ Shot3; Olympus). Following the puncture, the stylet was withdrawn and 0.75-mm micro biopsy forceps (Moray Micro forceps; STERIS) were introduced through the FNA needle. Targeted biopsy of the solid nodule was performed thrice (Fig. 1D). The biopsy led to a diagnosis of PNEN (Fig. 2A, B), and pancreaticoduodenectomy was performed. The resected specimens showed densely proliferating small tumor cells in the cystic wall, confirming the diagnosis of PNEN (Fig. 2C, D). To the best of our knowledge, reports on EUS-TTNB for PNEN with cystic degeneration are few, and this case highlights its utility in preoperative diagnosis. We obtained approval of an informed consent waiver from the Institutional Ethics Committee of the Shizuoka Cancer Center (approval number: J2023-253-2023-1-3).