A 22-year-old woman presented with fever, chills, photophobia, and headaches, followed by a centrally clearing erythematous skin eruption, migratory polyarthralgias, conjunctivitis, and subsequently, tender, nodular skin lesions. Antibodies to Borrelia burgdorferi were consistent with acute Lyme disease. Skin biopsy revealed acute septal panniculitis. This dermatologic manifestation has not been previously described in Lyme disease.