Objective: To assess useful CT features for differentiating benign from premalignant and malignant macrocystic pancreatic lesions. Methods: Seventy-four patients with pathologically proven macrocystic pancreatic lesions were enrolled: 17 benign cysts (macrocystic serous cystadenoma, n = 12; congenital cyst; n = 5) and 57 premalignant and malignant cysts (mucinous cystic neoplasm, n = 28; intraductal papillary mucinous neoplasm of branch duct type, n = 20; tumor with cystic change, n = 9). Size, location, shape (lobulated, round or oval, or complex cystic with tubular cyst), wall thickness (thin, <= 1 mm; thick, >1 mm), internal surface (smooth or irregular), and other findings were analyzed with multiphasic CT with thin-section (2.5-3 mm) images. CT features between two groups were compared using univariate and multivariate stepwise logistic regression analyses. Results: On univariate analysis, the differences for the shape (p = 0.007), wall thickness (p = 0.011), and internal surface (p = 0.012) between benign and premalignant and malignant cysts were significant. A lobulated shape, a thin wall and a smooth internal surface were more frequent in benign cysts, whereas a round or oval shape or a complex cystic shape with tubular cyst, a thick wall and an irregular internal surface were more frequent in premalignant and malignant cysts. On multivariate analysis, the shape (p = 0.002) and wall thickness (p = 0.025) were significant CT features for differentiating benign from premalignant and malignant cysts. Conclusion: Shape and wall thickness are the main CT features for differentiating benign from premalignant and malignant macrocystic pancreatic lesions. (C) 2008 Elsevier Ireland Ltd. All rights reserved.