We consider mitral valve disease requiring surgery in a patient with dextrocardia and situs inversus totalis to be an exceptional finding. The transseptal approach for mitral valve surgery in dextrocardia represents a technical challenge owing to its anatomic particulars. We present the case of a 56-year-old female patient who had been diagnosed with situs inversus totalis in childhood and with chronic atrial fibrillation in adulthood and was under oral anticoagulant treatment. She was referred to our hospital for increasing dyspnea and palpitation. Transthoracic echocardiography detected severe mitral regurgitation associated with moderate tricuspid regurgitation, with normal left and right ventricular function. Contrast chest computed tomography (CT) and preoperative abdominal CT showed both dextrocardia and situs inversus totalis, with normal continuity of the inferior vena cava. Biatrial cannulation was performed with the surgeon standing on the right side of the patient, and mitral valve replacement using a transseptal approach was performed with the surgeon standing on the left side of the patient. In this case report, we emphasize the rarity of mitral valve disease in a patient with dextrocardia and the inherent potential difficulty that can appear in this particular anatomic condition.