Neoadjuvant treatment for colon cancer could provide the advantages already demonstrated in rectal cancer. The FOxTROT trial examined neoadjuvant chemotherapy for locally advanced colon cancer based on CT imaging compared with initial surgery followed by postoperative chemotherapy. Neoadjuvant treatment was associated with reduced toxicity, significant downstaging leading to a greater rate of pathologically negative surgical resection margins and reduced 2-year recurrence rates. While overtreatment might in part explain the results, the data support the use of neoadjuvant chemotherapy in this colon cancer subpopulation.