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We report two patients with low-grade malignant primary cutaneous B cell lymphoma in association with Borrelia burgdorferi infection. Extracutaneous manifestations were ruled out by standard staging procedures. Infection with Borrelia burgdorferi was confirmed by cultivation from lesional skin in both patients. In the first patient skin lesions cleared completely after pulse therapy with cefotaxime, whereas in the second patient antibiotic treatment failed. In this patient, however, skin lesions completely cleared after intralesional injection of interferon alfa-2a. Antibiotic treatment or intralesional injection of interferon alfa-2a should be considered as a first-line treatment of Borrelia burgdorferi-associated primary cutaneous B cell lymphoma before more aggressive conventional therapeutic modalities (e.g., radiation therapy) are applied.