OBJECTIVE The aim of this study was to evaluate the accuracy of the activity quantification of single-photon emission computed tomography/computed tomography (SPECT-CT) (90)Y-Bremsstrahlung images and to validate the S-voxel method. METHODS An anthropomorphic torso phantom with radioactive inserts ((90)Y) was acquired by SPECT-CT. Constant calibration factors (cps/MBq) for the quantification were evaluated, considering different volume, shape, position inside the phantom, activity concentration and background, and distance from detectors. S-voxel values (EGSnrc) were implemented in MATLAB R0086 USA software. Dose comparisons between S-voxel and the conventional Medical Internal Radiation Dose method were repeated in a group of 11 patients administered with (90)Y-DOTATATE. RESULTS Using the appropriate calibration factors to recover the volume variability, the error about the measurement repeatability and the activity variation was within 4%. The variability of activity quantification, depending on the position in the phantom, detector distance, and background, was <10%, <5%, and <10%, respectively. The absorbed-dose values calculated by OLINDA were in agreement with the mean dose values obtained by the S-voxel method (difference, <10%). CONCLUSIONS The results confirm that, with the hybrid SPECT-CT system, quantitative analysis of SPECT (90)Y-Bremsstrahlung images and the generation of three-dimensional dose distributions are feasible. The improved analysis of Bremsstrahlung images could have a notable clinical impact, allowing to address the dosimetric verification to patients during the course of therapy.