An approach to the deformable registration of three-dimensional brain tumor images to a normal brain atlas is presented. The approach involves the integration of three components: a biomechanical model of tumor mass-effect, a statistical approach to estimate the model's parameters, and a deformable image registration method. Statistical properties of the sought deformation map from the atlas to the image of a tumor patient are first obtained through tumor mass-effect simulations on normal brain images. This map is decomposed into the sum of two components in orthogonal subspaces, one representing inter-individual differences in brain shape, and the other representing tumor-induced deformation. For a new tumor case, a partial observation of the sought deformation map is obtained via deformable image registration and is decomposed into the aforementioned spaces in order to estimate the mass-effect model parameters. Using this estimate, a simulation of tumor mass-effect is performed on the atlas image in order to generate an image that is similar to tumor patient's image, thereby facilitating the atlas registration process. Results for a real tumor case and a number of simulated tumor cases indicate significant reduction in the registration error due to the presented approach as compared to the direct use of deformable image registration.