In this paper, we present an evaluation study of a set of registration strategies for the alignment of sequences of 3D dynamic contrast-enhanced magnetic resonance breast images. The accuracy of the optimal registration strategies was determined on unseen data. The evaluation is based on the simulation of physically plausible breast deformations using finite element methods and on contrast-enhanced image pairs without visually detectable motion artifacts. The configuration of the finite element model was chosen according to its ability to predict in vivo breast deformations for two volunteers. We computed transformations for ten patients with 12 simulated deformations each. These deformations were applied to the postcontrast image to model patient motion occurring between pre- and postcontrast image acquisition. The original precontrast images were registered to the corresponding deformed postcontrast images. The performance of several registration configurations (rigid, affine, B-spline based nonrigid, single-resolution, multi-resolution, and volume-preserving) was optimized for five of the ten patients. The images were most accurately aligned with volume-preserving single-resolution nonrigid registration employing 40 or control point spacing. When tested on the remaining five patients the optimal configurations reduced the average mean registration error from 1.40 to for the whole breast tissue and from 1.20 to for the enhancing lesion. These results were obtained on average within 26 for 40 control point spacing. The visual appearance of the difference images from 30 patients was significantly improved after volume-preserving single-resolution nonrigid registration in comparison to no registration or rigid registration. No substantial volume changes within the region of the enhancing lesions were introduced by this nonrigid registration.