Alemtuzumab is a humanized anti-CD52 monoclonal antibody indicated for treatment of fludarabine-refractory B-cell chronic lymphocytic leukemia (B-CLL). Severe lymphopenia is one of the most profound hematologic effects of alemtuzumab, often predisposing patients to infectious complications such as herpes simplex virus, cytomegalovirus, and Pneumocystis jiroveci pneumonia. Opportunistic infections secondary to mycobacterial sources have been documented less frequently. We describe the case of a 46-year-old man who developed a 40-mm lymph node mass 4 months after completing alemtuzumab therapy. After a thorough evaluation, he began treatment for tuberculosis with a four-drug combination regimen. The patient's final biopsy report indicated the presence of Mycobacterium avium complex. All clinical signs of the infection resolved with no recurrence. To our knowledge, this is the first published report of a patient who developed M. avium complex after alemtuzumab therapy. Consideration of primary prophylaxis against M. avium complex infections in aggressively treated patients with advanced B-CLL or other clinical indications may be warranted if future reports of such atypical infections emerge.