This article describes the preparation, quality control, and biological evaluation of (90)Y-skin patches based on Nafion(®) membrane as a viable treatment modality for superficial skin tumors such as melanoma. To arrive at the conditions for optimum uptake of (90)Y on the membrane, influence of various experimental parameters, such as pH of the feed solution, inactive yttrium carrier concentration, reaction volume, contact time, and temperature, was systematically investigated. Under the optimized conditions, >95% of the (90)Y activity (37-185 MBq) could be incorporated in the Nafion membranes to prepare (90)Y-skin patches. Quality control tests were carried out to ensure nonleachability, uniform distribution of activity, and stability of the (90)Y-patches. Mice bearing transplanted melanoma tumors that were treated with two doses of 74 MBq (90)Y-Nafion membrane sources showed complete tumor regression. Histopathological examination of the treated area showed absence of tumor. The results of the study indicate the potential of (90)Y-Nafion membrane sources for treatment of superficial skin tumors.