Background <p>Situs inversus totalis (SIT) is a rare congenital anomaly characterized by the complete reversal of the major thoracic and abdominal visceral organs from their normal positions. The coexistence of SIT and lung cancer is exceedingly uncommon, posing significant challenges to surgeons due to increased surgical complexity.</p> Case summary <p>We report the case of a 65-year-old male was hospitalized upon the discovery of pulmonary lesions. Computed tomography (CT) revealed ground-glass nodules in the upper lobe of the left lung, as well as multiple small nodules throughout the remaining lung. The preoperative diagnosis included pulmonary space-occupying lesions and pneumonia. Following a comprehensive preoperative assessment, video-assisted thoracoscopic surgery was proposed as a treatment modality. The patient was discharged on the fourth postoperative day.</p> Discussion <p>This paper underscores the necessity of meticulous preoperative anatomical evaluation and careful perioperative management to prevent intraoperative injuries and complications in patients with SIT.</p> Clinical trial number <p>Not applicable.</p>