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Pre-operative chemoradiotherapy (CRT) is a preferable treatment option for patients with locally advanced rectal cancer. However, few data are available regarding pre-operative CRT for locally advanced colon cancer. Here, we describe two cases of successful treatment with pre-operative CRT and establish evidence supporting this treatment option in patients with locally advanced colon cancer. In the first case, a 65-year-old woman was diagnosed with ascending colon cancer with duodenal invasion. In the second case, a 63-year-old man was diagnosed with a colonic-duodenal fistula due to transverse colon cancer invasion. These case reports will help to establish a treatment consensus for pre-operative CRT in patients with locally advanced colon cancer.