Objective To explore clinical characteristics and therapeutic strategy of undifferentiated pleomorphic sarcoma of colon. Methods A retrospective study of 3 patients with undifferentiated peomorphic sarcoma of the colon was conducted. These cases were treated at the Peking Union Medical College Hospital from October 1983 to July 2016. In addition, the clinicopathologic data of 23 patients with undifferentiated pleomorphic sarcoma of colon reported in the literatures were analyzed. Results These 3 cases all received surgery in our hospital, including two patients who received postoperative radiotherapy. These three cases died of the local relapse or metastasis respectively at 5 months, 3 years, and 5 years after surgery. The 23 patients reported in the literatures were treated surgically except for 1 case, of which received chemotherapy after operation in the 2 cases, did not receive adjuvant therapy after operation in the 15 cases, were not reported clearly in the 6 cases. Sixteen cases had the results of follow-up, of which 9 cases had no recurrences or metastases and 7 cases died. Conclusions Undifferentiated pleomorphic sarcoma of colon has no specific clinical manifestation, it’s prognosis is very poor. Surgery is a main treatment for it at present. Thorough resection of tumor at an early stage is essential to patient’s recovery. Treatments such as chemotherapy and radiotherapy could be selected as postoperative adjuvant treatment, however, therapeutic schemes and effectiveness need further to be studied.