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Abstract Background Intra-arterial chemotherapy (IAC) has been used to treat multiple cancers including liver metastasis from uveal and cutaneous melanoma but not as primary tumor treatment. We report the compassionate use of chemoreduction with intra-arterial melphalan before ruthenium brachytherapy to salvage an eye with choroidal melanoma. Case presentation A 61-year-old female patient complained of decreased vision and central-temporal scotoma in OS (left eye) for 1 month. Visual acuity was 20/20 in right eye (OD) and 20/125 OS. Anterior segment examination and intraocular pressure were unremarkable in both eyes, as was fundus examination of the OD. Fundus examination of OS revealed a brown, solid tumor partially obscuring the temporal optic disc margin and extending to the equatorial fundus midzone. Serous retinal detachment was present over the lesion and around it. Ultrasonography revealed a solid choroidal tumor with a largest basal diameter (LBD) of 13.0 mm and thickness of 10.4 mm. The tumor presented acoustic hollowness and a superimposing retinal detachment. After metastatic screening was negative, the patient underwent intra-arterial chemotherapy with melphalan. Three weeks later, her visual acuity was 20/200 and there was noticeable tumor regression to 11.9 mm (LBD) by 7.9 mm (thickness) allowing brachytherapy to be performed. Ten weeks after brachytherapy (13 weeks after IAC), visual acuity was HM due to biopsy-related vitreous hemorrhage (VH). Tumor dimensions were 9.9 (LBD) mm and 6.5 mm (thickness) and PPV was performed to remove VH. Six weeks after PPV (20 weeks after IAC), her visual acuity was 20/200 and further reduction of tumor dimensions was observed: largest basal diameter was 8.9 mm and thickness was 4.9 mm. Conclusion This case illustrates the feasibility of combining induction IAC prior to ruthenium brachytherapy for large choroidal melanoma. More studies are warranted to confirm these early preliminary findings.