The aim of this study was to elucidate the regional differences between brain perfusion single photon emission computed tomography (SPECT) images reconstructed with a uniform attenuation correction using Chang's method (AC-Chang) and a non-uniform attenuation correction with CT using SPECT/CT (AC-CT). SPECT images of a phantom with and without head holder were obtained, and reconstructed images of AC-Chang and AC-CT were compared. Twenty-eight consecutive patients with brain disease examined by SPECT/CT brain perfusion imaging were selected, and images were reconstructed with AC-Chang and AC-CT. The AC-Chang and AC-CT reconstructed images were then compared by voxel-based analysis using three-dimensional stereotactic surface projections. Counts in the frontal area of the AC-Chang phantom image with head holder were higher than those in the posterior area. Counts in the frontal area of the AC-Chang clinical images were significantly higher than those in the AC-CT images, while the counts in the margin of the frontal lobe and posterior margin of the parietal, occipital cortices and cerebellum of the AC-Chang images were significantly lower. Relative frontal perfusion was 5.0% higher and relative cerebellar perfusion was 4.6% lower in the AC-Chang images relative to the AC-CT images, on average. We demonstrated the frontal dominant hyper-perfusion and parieto-occipital and cerebellar hypo-perfusion in brain SPECT images reconstructed with AC-Chang compared to those reconstructed with AC-CT. We suggest that to obtain an accurate attenuation-corrected brain perfusion SPECT image, attenuation correction by Chang's method is inadequate.