A 57-yr-old female patient was referred to our hospital with a cystic lesion of the head of the pancreas that had been noted on abdominal computed tomography (CT). Endoscopic ultrasonography (EUS) showed a 3.0 cm rounded mass in the head of the pancreas. EUS images showed that the tumor had a solid component consisting of multiple microcysts separated by septae and a cystic component consisting of a macrocystic lesion. Thus, the tumor was suspected of being a serous cystadenoma (SCA). However, the histopathological diagnosis based on endoscopic ultrasound- guided fine-needle-aspiration biopsy (EUS-FNAB) was that of a pancreatic endocrine neoplasm (PEN). Surgical resection was performed. Despite having very similar macroscopic findings to SCA, microscopic examination revealed that the patient's tumor was definitely a PEN. This case suggests that it is very difficult to distinguish PENs from SCAs based solely on imaging methods. EUS-FNAB is essential for determining the appropriate therapeutic strategy, as it provides the histopathological diagnosis.