A nodule registration system useful for tracking lung nodules in computed tomography (CT) scans is presented. The system registers a small sphere centered on a detected nodule in one scan with another scan under a rigid transformation assumption using a fast registration scheme. The registration scheme employs very fast simulated annealing (VFSA) with constraints to maximize a tunable cross-correlation (TCC) coefficient, enabling the system to register, with minimal registration error, all nodules within their maximum diameter. The system achieves an average registration time of 10 seconds or less on a 3.06 GHz computer programmed to implement the present invention.