In 2008, bacilli from 2 Hansen disease (leprosy) cases were identified as a new species,Mycobacterium lepromatosis. We conducted a systematic review of studies investigatingM. lepromatosisas a cause of HD. Twenty-one case reports described 27 patients with PCR–confirmedM. lepromatosisinfection (6 dualM. leprae/M. lepromatosis): 10 case-patients in the United States (7 originally from Mexico), 6 in Mexico, 3 in the Dominican Republic, 2 each in Singapore and Myanmar, and 1 each in Indonesia, Paraguay, Cuba, and Canada. Twelve specimen surveys reported 1,098 PCR–positive findings from 1,428 specimens, includingM. lepromatosisin 44.9% (133/296) from Mexico, 3.8% (5/133) in Colombia, 12.5% (10/80) in Brazil, and 0.9% (2/224) from the Asia-Pacific region. Biases toward investigatingM. lepromatosisas an agent in cases of diffuse lepromatous leprosy or from Mesoamerica precluded conclusions about clinicopathologic manifestations and geographic distribution. Current multidrug treatments seem effective for this infection.