Image registration of multimodality images is an essential task in numerous applications in three-dimensional medical image processing. Medical diagnosis can benefit from the complementary information in different modality images. Surface-based registration techniques, while still widely used, were succeeded by volume-based registration algorithms that appear to be theoretically advantageous in terms of reliability and accuracy. Several applications of such algorithms for the registration of CT-MRI, CT-PET, MRI-PET, and SPECT-MRI images have emerged in the literature, using local optimization techniques for the matching of images. Our purpose in this work is the development of automatic techniques for the registration of real CT and SPECT images, based on either surface- or volume-based algorithms. Optimization is achieved using genetic algorithms that are known for their robustness. The two techniques are compared against a well-established method, the Iterative Closest Point-ICP. The correlation coefficient was employed as an independent measure of spatial match, to produce unbiased results. The repeated measures ANOVA indicates the significant impact of the choice of registration method on the magnitude of the correlation (F = 4.968, p = 0.0396). The volume-based method achieves an average correlation coefficient value of 0.454 with a standard deviation of 0.0395, as opposed to an average of 0.380 with a standard deviation of 0.0603 achieved by the surface-based method and an average of 0.396 with a standard deviation equal to 0.0353 achieved by ICP. The volume-based technique performs significantly better compared to both ICP (p<0.05, Neuman Keuls test) and the surface-based technique (p<0.05, Neuman-Keuls test). Surface-based registration and ICP do not differ significantly in performance.