We report a 41-year-old patient with multiple sclerosis (MS) who was successfully desensitized after she developed non-injection-site urticaria and angioedema due to interferon (IFN)-β1a. Although a few cases of urticaria and anaphylaxis have been reported in the literature, to our knowledge this is the first report of a successful desensitization with IFN-β1a. Desensitization with IFN-β1a allowed us to continue with the administration of interferon-β, which is a mainstay in treatment for MS.