Objective To investigate the pathological features, diagnosis, treatment, and prognosis of multiple primary colorectal cancer (MPCC). Methods Clinical data of 41 patients with MPCC treated in The Fourth Affiliated Hospital and The First Affiliated Hospital of China Medical University from Aug. 1993 to Mar. 2009 were retrospectively analyzed. Results Forty one patients with MPCC, including 29 patients with synchronous colorectal cancer (SCC) and 12 patients with metachronous colorectal cancer (MCC), accounted for 1.8% (41/2 340) of colorectal cancer during the same period of time, and with adenomatous polyps in 19 cases and polyps canceration in 10 cases. Among 29 patients with SCC, 15 cases (51.7%) were diagnosed by preoperative fiberoptic colonoscopy, 9 cases (31.0%) were diagnosed by preoperative fiberoptic colonoscopy, abdomen CT, and barium enema, 5 cases (17.2%) were diagnosed by intraoperative exploration and intraoperative fiberoptic colonoscopy, respectively. All of the 12 patients with MCC were diagnosed by preoperative fiberoptic colonoscopy and abdomen CT. For 29 patients with SCC, tumor locations were from proximal appendix to distal rectum, but 12 patients with MCC were adverse. Sixty-five (77.4%) tumors were tubular or papillary adenocarcinoma, and 56 (66.7%) tumors were well and moderately differentiated adenocarcinoma. The TNM stage of most tumors (72) was stageⅡ or Ⅲ phase, account for 85.7%. Radical surgeries were performed in 37 patients and palliative surgeries in 4 patients, and there were no complications after operation. During the follow-up for 3-5 years (mear 3.6 years), the overall survival rate of 3- and 5-year were 48.8% (20/41) and 34.1% (14/41), respectively. In detail, 3-year survival rate of SCC group and MCC group were 48.3% (14/29) and 50.0% (6/12), respectively;5-year survival rate were 31.0% (9/29) and 41.7% (5/12), respectively. Conclusions Cause of MPCC has not been clear, but it has possible relationship with adenomatous polyps. Preoperative fiberoptic colonoscopy, abdomen CT, and barium enema are very important for patients with SCC, and intraoperative fiberoptic colonoscopy is also necessary. Patients with MCC should enhance postoperative follow-up with fiberoptic colonoscopy. Further more, radical resection should be performed as early as possible.