A method and system of volume segmentation is disclosed. To address throughput speed and accuracy requirements, the segmentation is divided into two stages: presegmentation and detailed segmentation. In presegmentation, a digital image volume is processed to identify anatomical structures from image backgrounds in a gross manner possibly at reduced image resolution. Detailed segmentation then involves refining and segmenting further the fine details within the anatomical structures identified by presegmentation. One result of the overall volume segmentation algorithm is a volume in which segmented regions of interest, such as nodules, are identified.