This note describes a method to characterize the performances of image fusion software (Syntegra) with respect to accuracy and robustness. Computed tomography (CT), magnetic resonance imaging (MRI), and single-photon emission computed tomography (SPECT) studies were acquired from two phantoms and 10 patients. Image registration was performed independently by two couples composed of one radiotherapist and one physicist by means of superposition of anatomic landmarks. Each couple performed jointly and saved the registration. The two solutions were averaged to obtain the gold standard registration. A new set of estimators was defined to identify translation and rotation errors in the coordinate axes, independently from point position in image field of view (FOV). Algorithms evaluated were local correlation (LC) for CT-MRI, normalized mutual information (MI) for CT-MRI, and CT-SPECT registrations. To evaluate accuracy, estimator values were compared to limiting values for the algorithms employed, both in phantoms and in patients. To evaluate robustness, different alignments between images taken from a sample patient were produced and registration errors determined. LC algorithm resulted accurate in CT-MRI registrations in phantoms, but exceeded limiting values in 3 of 10 patients. MI algorithm resulted accurate in CT-MRI and CT-SPECT registrations in phantoms; limiting values were exceeded in one case in CT-MRI and never reached in CT-SPECT registrations. Thus, the evaluation of robustness was restricted to the algorithm of MI both for CT-MRI and CT-SPECT registrations. The algorithm of MI proved to be robust: limiting values were not exceeded with translation perturbations up to 2.5 cm, rotation perturbations up to 10 degrees and roto-translational perturbation up to 3 cm and 5 degrees.