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Introduction: Right-sided colon cancer(RSCC) and left-sided colorectal cancer(LSCRC) differ with respect to their biology and genomic patterns. This study aimed to examine whether the primary tumor location is associated with the response to cetuximab in patients with metastatic colorectal cancer(m CRC).Methods: Patients with mC RC treated with cetuximab and standard chemotherapy as first- or second-line treatments were compared with randomly chosen patients who were treated with chemotherapy alone between 2005 and 2013.The main outcome measures were the overal response rate(ORR), progression-free survival(PFS), and overal survival(OS).The differences in the outcome were analyzed by using the chi-squared test, Student’s t test, and Kaplan-Meier method.Results: The treatment results of 206 patients with m CRC treated with cetuximab and standard chemotherapy as first- or second-line treatments were compared with those of 210 patients who were treated with chemotherapy alone. As a first-line treatment, cetuximab with chemotherapy was associated with a significantly higher ORR(49.4 % vs. 28.6 %, P = 0.005) as well as longer PFS(9.1 vs. 6.2 months, P = 0.002) and OS(28.9 vs. 20.1 months,P = 0.036) than chemotherapy alone in patients with LSCRC. However, cetuximab neither improved the ORR(36.4 % vs. 26.2 %, P = 0.349) nor prolonged PFS(5.6 vs. 5.7 months, P = 0.904) or OS(25.1 vs. 19.8 months, P = 0.553) in patients with RSCC. As a second-line treatment, cetuximab exhibited a tendency to improve the ORR(23.5 % vs. 10.2 %,P = 0.087) and prolong PFS(4.9 vs. 3.5 months, P = 0.064), and it significantly prolonged OS(17.1 vs. 12.4 months,P = 0.047) compared with chemotherapy alone in the patients with LSCRC. In contrast, as a second-line treatment,cetuximab neither improved the ORR(7.1 % vs. 11.4 %, P = 0.698) nor prolonged PFS(3.3 vs. 4.2 months, P = 0.761) or OS(13.4 vs. 13.0 months, P = 0.652) in patients with RSCC.Conclusions: The addition of cetuximab to chemotherapy in both first- and second-line treatments of m CRC may only benefit patients with primary LSCRC.