We report two pediatric retinoblastoma patients with unusual ophthalmic artery (OA) origins who were referred to our interventional neuroradiology department for intraarterial chemotherapy. The first patient had double OAs arising from the ipsilateral internal carotid artery and a central retinal artery (CRA) arising from the more cranially located artery, whereas the second patient had an OA originating from the A1 segment of the ipsilateral anterior cerebral artery. In both cases the CRA arose from the artery entering the orbit through the optic foramen. Both patients tolerated the procedures well. To the best of our knowledge, our retinoblastoma patients with unusual OA origins are the first in the literature in which detailed knowledge of the orbital vasculature and especially CRA origin carried immediate clinical implications, altering access strategies. These variations were proved both by flat-panel detector computed tomography findings and superselective injections of OAs with unusual origins. Our results show that in patients with retinoblastoma, a detailed angiographic work-up may be necessary to evaluate the orbital vasculature and possible abnormal origin of the OA. Recognition of possible variations of OA origin and its branching patterns is of the utmost importance for successful treatment and avoidance of adverse events among retinoblastoma patients.