Although the clinical, radiologic and pathologic features of cystic pancreatic lesions are well known, preoperative diagnosis is difficult. Differentiation between a pancreatic pseudocyst and a cystic pancreatic neoplasm is crucial in determining the proper treatment. Objectives: This study focuses on our experience in the diagnosis and differentiation of cystic pancreatic lesions by using invasive manipulations under imaging- US and CT control. Methods: 128 biopsies and punctures of pancreatic cystic lesions in 105 patients /73 male and 32 female/ were performed under US and CT control for a period of 5 years. Lesions ranged in diameter from 15mm to 140mm. We utilized US guidance in 97/75.78%/ and CT guidance in 31/24.21%/ of all 128 biopsies. Results: In all 128 diagnostic biopsies and punctures of cystic pancreatic lesions performed under imaging control a sufficient material for cytological and histological examination were obtained. 81 pseudocysts, 8 serous and mucinous cystic neoplasms, 18 cystadenocarcinomas and 4 solide and papillary epithelial neoplasms were proven. Conclusions: Based on the obtained results and literature reports we propose biopsy under imaging/US and CT/ control as a method with high diagnostic accuracy in differentiating preoperatively cystic pancreatic lesions.