An 86-year-old woman presented with osteonecrosis of the mandible following bisphosphonate therapy for multiple myeloma, and underwent surgical debridement and multiple dental extractions. Histopathologic examination of the necrotic bone fragments revealed acute osteomyelitis with mixed flora and organisms morphologically consistent withEntamoeba gingivalis. In addition to oral scrapings and sputum,E. gingivalishas been identified in specimens obtained from the uterus, cervix, neck lymph nodes, and lung. It is rarely found in lesions of the head and neck. We present an unusual case ofE. gingivalisin acute osteomyelitis of the mandible, following bisphosphonate therapy for multiple myeloma. To our knowledge, this is the first reported case ofE. gingivalisin association with osteomyelitis.