The present study was aimed at distinguishing halogen atoms substituted in a molecule of copper-phthalocyanine (CuPc) by high-resolution transmission electron microscopy (HRTEM). The subject was carried out on octabromooctachloro-CuPc and obtained HRTEM images suggested inhomogeneous distribution of bromine and chlorine atoms at 1-, 2-, 3- and 4-substitution positions of CuPc in image contrast. As a result of electron crystallography, the occupancy of bromine atoms at the 1-position (and equally at the 4-position) was found to be 52%, which is slightly higher than for random substitution. This small deviation causes apparent inhomogeneous image contrast of halogen substitution observed in the high-resolution images, as concluded from computer simulation of images. Such potential to detect inhomogeneity in substitution by TEM should be important for the chemical understanding of substitution reactions at the atomic level.