Objective To summarize the current status and challenges in the diagnosis and treatment of colorectal cancer (CRC) in patients with situs inversus totalis (SIT) , and to provide insights for clinical diagnosis and treatment. MethodsBy literature researching, we systematically reviewed the clinical manifestations, molecular pathogenesis, individualized surgical strategies, and prognosis of SIT-CRC. ResultsCurrent studies indicate a general lack of awareness of SIT-CRC, and its mirror-image anatomy significantly increases diagnostic and therapeutic challenges. SIT-CRC is extremely rare, with tumors predominantly located in the sigmoid colon and ascending colon. Molecular studies suggest that SIT-CRC may harbor unique genetic mutation profiles. Treatment involves using systematic preoperative assessment of vascular variations using three-dimensional CT angiography, multidisciplinary team discussions, and implementation of individualized surgical planning. Postoperative attention should be paid to complication management, individualized adjuvant therapy, and long-term follow-up. ConclusionEnhancing the awareness of SIT-CRC and adopting a systematic, multidisciplinary, and individualized approach are crucial for optimizing patients’ outcomes.