The etiology of morphea is poorly understood, but small vessel endothelial damage, T-cell recruitment, immune dysregulation, and the release of profibrotic cytokines likely contribute to pathogenesis. Biologic agents such as interferon (IFN)-β1α influence the development of systemic sclerosis (SSc) in patients with multiple sclerosis (MS). Treatment with type I interferons, such as IFN-β1α, may activate shared pathogenic pathways of autoimmunity and promote the development of morphea. We present the case of a 55-year-old female who developed morphea secondary to IFN-β1α therapy for multiple sclerosis. This article is protected by copyright. All rights reserved.