Objective To investigate the clinical features, diagnosis and management of pancreatic lesions in patients with von Hippel-Lindau (VHL) disease, and improve the current understanding on pancreatic lesions in VHL disease.Methods The clinical data of three VHL disease patients with pancreatic lesions were analyzed retrospectively, including clinical features, laboratory findings, imaging, pathological features, operation method and follow-up.Results Two patients had a family history of hemangioblastoma in central neural system, and 1 patient had retinal multiple angioma and angioma in central neural system, who were diagnosed as VHL.One patient with pancreatic portal hypertension had splenectomy and biopsy of left renal tumor.During the surgery, pancreatic cystic lesions were observed and the transparent cysts were diffusively distributed on the surface.The other 2 patients were diagnosed as pancreatic multiple cysts and non functional pNETs, and pancreatic multiple cysts, respectively, based on the imaging.All the three patients had stable disease status, and followed up by outpatient visits.Conclusions VHL disease can manifest as simple pancreatic cyst, pancreatic serous cystadenoma and pNETs.The optimal individualized treatment should be determined by Multidisciplinary team (MDT) according to the general condition of patient.