Heterotaxic disorders or situs ambiguus are uncommon anatomical variations constituted by a partial mirror-image disposition of intra thoracic and/or abdominal solid organs. These variations are challenging because rarely met in a surgeon's career, and because of the coexistence of numerous other anatomical variants, like ones related to the asymmetrical organs, causing difficulties when a surgical management is required. We report the case of a 57-year-old patient presenting liver cirrhosis in which regular follow-up discovered a hepatocellular carcinoma of the right part of the liver associated to numerous anatomical variations in the setting of a situs ambiguus. This patient was successfully treated by a sub-segmentectomy via a right sub-costal laparotomy. There were neither peroperative nor postoperative complications. This case emphasizes the technical difficulties faced, successfully managed thanks to a good preoperative screening, and allows us to review literature of such a rare and challenging situation.