Vaccine-induced cutaneous lymphoid hyperplasia (CLH) is rare. Its natural evolution is not well known, nor is its treatment. We report a case of B-cell CLH with secondary dissemination that occurred following vaccination. The symptoms lasted 12 years and were efficiently treated by thalidomide. A 17-year-old girl presented CLH which had begun at the age of 8 at the site of hepatitis B vaccination. The lesions progressively enlarged and disseminated far from the injection sites. There was no spontaneous remission. Cyclins and hydroxychloroquine were inefficient. Thalidomide treatment finally led to complete remission. Aluminium hydroxide is used as adjuvant in the majority of vaccinations. In this case, occurrence of lesions far from the injection site of the vaccine suggested that it was not the only cause and that CLH may occur in other localizations after a vaccination. Furthermore, the diagnosis of CLH should not be excluded in front of such a prolonged course, and we underline the potential efficacy of thalidomide.