We describe a 54-year-old woman with diffuse myxoedematous infiltration at the site of a smallpox vaccination scar as the presenting symptom of Graves' disease. Associated features included acute ocular symptoms (vascular congestion of the sclera, epiphora and blurred vision) and transient erythema on both shins. However, there were no signs of pretibial myxoedema. A number of neoplastic, inflammatory and systemic diseases may localize to scar tissue in skin, including at smallpox vaccination sites, but this case demonstrates the unusual occurrence of myxoedematous infiltration at such a site and illustrates a most atypical cutaneous presentation of Graves'disease.