Mycobacterium ulcerans infection causes a skin disease known as Buruli ulcer (BU), a disorder manifested usually as a solitary and painless nodule or papule that progresses to massive necrotizing destruction and cutaneous ulceration. When healing occurs, it often results in disabling deformities. Buruli ulcer is considered the third most common mycobacterial disease in immunocompetent people, after tuberculosis and leprosy. Although the emergence of Buruli ulcer in Western African countries over the past decade has been dramatic, it has been scarcely reported in industrialized countries. We report a patient from Equatorial Guinea who was human immunodeficiency virus-positive, presenting aggressive and multifocal BU associated with an underlying destructive osteomyelitis, in which only an aggressive surgical approach yielded to a resolution of the disease. In a global world, with increasing migratory population fluxes, an increased awareness of dermatologists regarding the clinical, histopathological and microbiological features of BU is important in order to avoid significant delays in diagnosis and treatment.