Yttrium-90 ((90)Y)-microspheres administered via the hepatic artery has been used for the treatment of unresectable primary or metastatic cancer in the liver. Prior to (90)Y therapy, however, the (90)Y administered activity and the percent shunting to lungs must be determined, most commonly by gamma camera imaging of technetium-99m ((99m)Tc)-macroaggregated albumin (MAA). The purpose of the current study was to identify and evaluate an objective measure of the correlation of (90)Y and MAA activity distributions and thus assess the reliability of MAA imaging for evaluation of (90)Y administered activity and tumor and liver radiation doses. The MAA study consisted of two acquisitions. After administration of 185 MBq of MAA, a partial-body or so-called breakthrough scan was performed in order to determine the percent shunting to lungs. Immediately after a breakthrough scan, a combined single-photon emission computed tomography (SPECT)/transmission computed tomography (CT) scanner was used to image MAA distribution in order to derived the prescribed (90)Y administered activity based on tumor and liver dosimetry. (90)Y SPECT/CT was performed 2-4 weeks later and activities used were in the range of 777-2,442 MBq. In order to compare (90)Y and MAA SPECT images, first the respective CT image sets were registered using a transform based on normalized mutual information. The transform thus derived was used to align the 90Y and MAA SPECT image sets, and the Spearman's (rho) rank correlation as well as image distance (L2-norm) between the registered SPECT images were then calculated. The Spearman's rank correlation values ranged from 0.451 to 0.818 and the L2 distances from 0.626 to 2.889. Based on visual inspection, the registration of the (90)Y and MAA SPECT images appeared reasonably accurate. The regression coefficient (r) between visual scoring and the Spearman's rank correlation was 0.65 and between visual scoring and L2 distance 0.61. The Spearman's rank correlation thus appears to be more reliable than the image distance for assessing the correlation of the (90)Y and MAA images.