Purpose: Y-90-microsphere selective internal radiation therapy (Y-90-SIRT or Y-90-radioembolization) is used in the management of unresectable liver tumors. Y-90-SIRT presents a unique situation where the total Y-90 activity inside the liver can be determined with high accuracy (> 95%). Y-90 bremsstrahlung single-photon emission computed tomography (SPECT)/computed tomography (CT) can be self-calibrated to provide quantitative images that facilitate voxel-level absorbed dose calculations. We investigated the effects of different approaches for Y-90-SPECT self-calibration on the quantification of absorbed doses following Y-90-SIRT. Methods: Y-90 bremsstrahlung SPECT/CT images of 31 patients with hepatocellular carcinoma, collected following Y-90-SIRT, were analyzed, yielding 48 tumor and 31 normal liver contours. We validated the accuracy of absorbed doses calculated by a commercial software against those calculated using Monte Carlo-based radiation transport. The software package was used to analyze the following definitions of SPECT volume of interest used for Y-90-SPECT self-calibration: (a) SPECT field-of-view (FOV), (b) chest-abdomen contour, (c) total liver contour, (d) total liver contour expanded by 5 mm, and (e) total liver contour contracted by 5 mm. Linear correlation and Bland-Altman analysis were performed for tumor and normal liver tissue absorbed dose volume histogram metrics between the five different approaches for Y-90-SPECT self-calibration. Results: The mean dose calculated using the commercial software was within 3% of Monte Carlo for tumors and normal liver tissues. The tumor mean dose calculated using the chest-abdomen calibration was within 2% of that calculated using the SPECT FOV, whereas the doses calculated using the total liver contour, expanded total liver contour, and contracted total liver contour were within 68%, 47%, and 107%, respectively, of doses calculated using the SPECT FOV. The normal liver tissue mean dose calculated using the chest-abdomen contour was within 1.3% of that calculated using the SPECT FOV, whereas the doses calculated using the total liver contour, expanded total liver contour, and contracted total liver contour were within 73%, 50%, and 114%, respectively, of doses calculated using the SPECT FOV. Conclusions: The mean error of < 3% for commercial software can be considered clinically acceptable for Y-90-SIRT dosimetry. Absorbed dose quantification using Y-90-SPECT self-calibration with the chest-abdomen contour was equivalent to that calculated using the SPECT FOV, but self-calibration with the total liver contour yielded substantially higher (similar to 70%) dose values. The large biases revealed by our study suggest that consistent absorbed dose calculation approaches are essential when comparing Y-90-SIRT dosimetry between different clinical studies. (C) 2017 American Association of Physicists in Medicine