Immunosuppressive and immune-modulating substances such as corticosteroids, chloroquin, hydroxychloroquin, azathioprin, methotrexate, and others are standards in therapy of cutaneous lupus erythematosus. However, alternative substances are necessary when standard therapy regimens fail or are associated with side effects. Describing the course of disease in five female patients, we demonstrate alternative treatment of subacute cutaneous lupus erythematosus with thalidomide, showing good symptom response and possible side effects. By careful patient selection, we observed no polyneuropathy as it is most commonly described. In two cases, maculopapulous exanthema induced by medication was seen. The teratogeny of the substance must be taken into account in prescription. In selected cases, thalidomide can be a highly effective therapeutic option in the treatment of subacute cutaneous lupus erythematosus.