A patient with severe erythema nodosum due to Behçet's disease is reported on here. Erythema nodosum lesions did not respond to classical treatments; however, they cleared after erythromycin treatment, which was prescribed for the treatment of coincidental erythrasma. Erythromycin treatment appears to be an effective treatment option in erythema nodosum. The hypothetical anti-inflammatory effects of erythromycin, besides its antibiotic properties, are reviewed and discussed to explain such a clinical improvement.