Physicians often utilize different imaging techniques to provide clear, visual information about internal parts of the patient. Since the different imaging modalities give different types of information, the combination of them serves as a powerful tool while determining the diagnosis, planning of treatment or during therapy follow-up. To simplify the interpretation of the image information, image registration is often used. The goal of the registration is to put different images in a common coordinate system. It is essential that the registration between the images is accurate. Normalized Mutual Information (NMI) is a metric that quantifies the conformity between images. Even though NMI is a robust method it is often dominated by large structures as the external contour of the patient as well as by the structures of the bones. The prostate is an organ that does not have a fixed position relative to the other organs and host small amounts of image information. The accuracy of the registration is therefore limited with respect to the prostate when using the whole image volume. This master thesis investigates the possibility to restrict the part of the image used for registration to a small volume around the prostate with goal to receive a better registration of the prostate than if full sized images are used. A registration program, utilizing NMI, was written and optimized in MatLab. Four Magnetic Resonance (MR) series and one Computed Tomographic (CT) series where taken over the pelvic area of five patients with the diagnosis prostate cancer. The prostate were delineated by a physician. By adding margin to the delineations five different sized Regions of Interest (ROI) where created.  The smallest ROI precisely covered the prostate while the largest covered the whole image. The deviation in Center of Mass (CoM) between the images and the Percentage Volume Overlap (PVO) were calculated and used as a measure of alignment. The registrations performed with sub-volumes showed an improvement compared to those that used full-volume while registering a MR image to another MR image. In one third of the cases a 2 cm margin to the prostate is preferable. A 3 cm margin is the most favorable option in another third of the cases. The use of sub-volumes to register MR images to CT series turned out to be unpredictable with poor accuracy. Full sized image registration between two MR image pairs has a high precision but, due to the motion of the prostate, poor accuracy. As a result of the high information content in the MR images both high precision as well as high accuracy can be achieved by the use of sub-volume registration. CT images do not contain the same amount of image information around the prostate and the sub-volume based registrations between MR and CT images are hence inconsistent with a low precision.