This study investigates the bias between MNI and Talairach coordinates when using the ICBM-152 brain template. The research compares MNI coordinates derived from SPM2 and FSL/FLIRT with Talairach coordinates obtained via a landmark-based method. Analysis reveals a clear bias in reference frames (origin, orientation) and scaling (brain size). ICBM-152 fitted brains were consistently larger, oriented more nose-down, and translated slightly down relative to Talairach fitted brains. Whole brain analysis of coordinate disparity showed an ellipsoidal pattern with disparity ranging from zero at a point deep within the left hemisphere to greater than 1-cm for some anterior brain areas. MNI/Talairach coordinate disparity was generally less for brains fitted using FSL. The mni2tal transform generally reduced MNI/Talairach coordinate disparity for inferior brain areas but increased disparity for anterior, posterior, and superior areas. Coordinate disparity patterns differed for brain templates (MNI-305, ICBM-152) using the same fitting method (FSL/FLIRT) and for different fitting methods (SPM2, FSL/FLIRT) using the same template (ICBM-152). An MNI-to-Talairach (MTT) transform was formulated using a best-fit analysis in one hundred high-resolution 3-D MR brain images. MTT transforms optimized for SPM2 and FSL were shown to reduce group mean MNI/Talairach coordinate disparity from a 5-13 mm to 1-2 mm for both deep and superficial brain sites. MTT transforms provide a validated means to convert MNI coordinates to Talairach compatible coordinates for studies using either SPM2 or FSL/FLIRT with the ICBM-152 template.This study investigates the bias between MNI and Talairach coordinates when using the ICBM-152 brain template. The research compares MNI coordinates derived from SPM2 and FSL/FLIRT with Talairach coordinates obtained via a landmark-based method. Analysis reveals a clear bias in reference frames (origin, orientation) and scaling (brain size). ICBM-152 fitted brains were consistently larger, oriented more nose-down, and translated slightly down relative to Talairach fitted brains. Whole brain analysis of coordinate disparity showed an ellipsoidal pattern with disparity ranging from zero at a point deep within the left hemisphere to greater than 1-cm for some anterior brain areas. MNI/Talairach coordinate disparity was generally less for brains fitted using FSL. The mni2tal transform generally reduced MNI/Talairach coordinate disparity for inferior brain areas but increased disparity for anterior, posterior, and superior areas. Coordinate disparity patterns differed for brain templates (MNI-305, ICBM-152) using the same fitting method (FSL/FLIRT) and for different fitting methods (SPM2, FSL/FLIRT) using the same template (ICBM-152). An MNI-to-Talairach (MTT) transform was formulated using a best-fit analysis in one hundred high-resolution 3-D MR brain images. MTT transforms optimized for SPM2 and FSL were shown to reduce group mean MNI/Talairach coordinate disparity from a 5-13 mm to 1-2 mm for both deep and superficial brain sites. MTT transforms provide a validated means to convert MNI coordinates to Talairach compatible coordinates for studies using either SPM2 or FSL/FLIRT with the ICBM-152 template.