Erythema chronicum migrans (ECM) is the distinctive cutaneous lesion of the multisystem tick-borne spirochetosis, Lyme disease. Its clinical and histologic pictures are variable. Of the 51 patients with ECM of Lyme disease, 38 patients (75%) had single lesions, 13 patients (25%) had multiple lesions, and 32 patients (62%) had extracutaneous signs and symptoms. Only 15 patients (29%) had symptoms referable to ECM. Extracutaneous signs and symptoms were absent in 12 (80%) of the 15 patients. These patients had uneventful recoveries following treatment with systemic antibiotics. Thirty-four skin biopsy specimens were obtained from the ECM lesions of 30 patients. With Warthin-Starry silver stain, the Ixodes dammini spirochete was found in 14 specimens (41%) taken from 12 (40%) of the 30 patients. Two of the Ixodes dammini spirochete-positive specimens were obtained from secondary ECM lesions. Careful clinical and histologic examination of skin lesions suggestive of ECM of Lyme disease will expedite its early diagnosis and treatment.