Objective: We aimed to investigate the association between a family history (FH) of colorectal cancer (CRC) and cancer recurrence and survival in patients with stage III CRC. Methods: From April 2001 to December 2007, 1102 patients with stage III CRC were enrolled and their data including FH, clinicopathological characteristics of the tumor were retrospectively analyzed. Results: Of 971 patients that were finally enrolled, 63 (6.5%) reported CRC in at least one first-degree relative. Death occurred in 12.7% of the CRC patients with an FH and 21.8% in those without an FH. A multivariate analysis showed that patients with an FH of CRC, compared with those without FH, had an adjusted hazard ratios (HR) of 0.674 (P=0.281) for overall survival (OS) and 0.672 (P=0.220) for disease-free survival (DFS). However, the location of tumor, preoperative carcinoembryonic antigen (CEA) level, tumor invasion (T) stage and lymph node (N) metastasis significantly affected OS and DFS. Furthermore, whereas the FH of CRC patients was associated with a favorable prognosis in stage III colon cancer (HR 0.224, P=0.040) but not in rectal cancer (HR 1.225, P = 0.640). Conclusions: In patients with stage III CRC, tumor location (especially in the rectum), a high preoperative CEA level and advanced T and N stages indicate a poor prognosis. However, in stage III colon cancer FH is associated with improved survival. © 2013 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.