CT colonography (CTC) is a minimally invasive screening technique for colorectal polyps and colon cancer. Since electronic colon cleansing (ECC) cannot completely remove the presence of pseudo-polyps, most CTC protocols acquire both prone and supine images to improve the visualization of the lumen wall and to reduce false positives. Comparisons between the prone and supine images can be facilitated by computerized registration between the scans. In this paper, we develop a fully automatic method for registering colon surfaces extracted from prone and supine images. The algorithm uses shape spectrum to extract the shape characteristics which are employed as the surface signature to find the correspondent regions between the prone and supine lumen surfaces. Our experimental results demonstrate an accuracy of 12.6 ± 4.20 mm over 20 datasets. It also shows excellent potential in reducing the false positive when it is used to determine polyps through correspondences between prone and supi...