PURPOSE: To describe a case of cotton wool spots associated with interferon beta-1a treatment. METHODS: Observational case report. RESULTS: A 40-year-old man with a history of multiple sclerosis was on interferon beta-1a. He presented with cotton wool spots on fundus exam, which resolved and then recurred all while on therapy. Interferon was discontinued after the second episode and again the cotton wool spots resolved. Upon restarting the interferon, no further cotton wool spots have recurred. CONCLUSION: To our knowledge this represents only the third case of interferon beta-1a associated cotton wool patches and the first in the English-language ophthalmic literature. Unlike interferon alpha therapy, interferon beta 1-a retinopathy is presumed to be extremely rare and more common etiologies for cotton wool spots should be excluded in these patients. Given this limited number of cases versus the relatively frequent use of interferon beta-1a in the management of multiple sclerosis, no conclusions regarding causality or screening can be made but the issue probably deserves further study.