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Infective endocarditis, a serious microbial infection of the cardiac endothelial surface, may involve any heart valve. However, right-sided endocarditis is uncommon in non-intravenous drug abusers without underlying heart disease, and the contextual involvement of the left-sided valve is exceptional. A 63-year-old man with no evidence of intravenous drug abuse or heart disease, presented with persistent fever, worsening of breath, and aphasia. His medical history was notable for mild arterial hypertension and serious lymphangitis with cutaneous erosions on the legs. Transesophageal echocardiography was performed for suspicious endocarditis and showed a pedunculated and highly mobile vegetation adhered to the atrial portion of the posterior leaflet of the mitral valve, protruding into the left ventricle through the valvar orifice. Another large vegetation was seen at the tricuspid valve surface and protruded into the right ventricle during diastole. Cerebral and thoraco-abdominal computed tomography scan revealed multiple embolism to the left kidney, spleen, lungs and central nervous system. Blood cultures identified Staphylococcus aureus. The only risk factor was large skin sepsis. Despite successful antibiotic therapy, the patient died for development of renal and respiratory failure.