Aim: This prospective study was designed to evaluate the tolerability and the efficacy of bi-weekly SOX (S-1 and oxaliplatin)+cetaximab as first-line chemotherapy for wild-type K-RAS metastatic colorectal cancer. Patients and Methods: We studied patients with previously untreated, unresectable advanced or recurrent colorectal cancer who were treated in our hospital between October 2010 and March 2013. Their performance status (PS) was 0 to 1. Cetuximab was combined with S-1 and oxaliplatin (SOX+cetuximab). 51 was given orally at a dose of 40 mg/m(2) (40-60 mg, calculated according to body surface area) twice daily after meals for 2 weeks, followed by a 2-week rest (course 1). Oxaliplatin (85 mg/m2) was given on days 1 and 15 of each course. Cetuximab was administered on days 1 (400 mg/m(2)), 8 (250 mg/m2) and 15 (500 mg/m(2)) of course 1, followed by every 2 weeks (500 mg/m(2)) thereafter. Results: The study group comprised of 18 patients. The mean age was 61 (range=32-72) years, the male:female ratio was 10:8 and the PS was 0 in 12 patients and 1 in 6 patients. The median number of administered courses was 6 (range=2-12). The treatment response was complete response (CR) in 2 and partial response (PR) in 10 (response rate=67% (12/18 patients)). The minimum number of treatment courses until a PR was 2, indicating an early response. Liver resection was performed in 4 patients (22.2%). The incidence of any adverse events (Grade 314) was 28% (5/18), including skin disorder (16.7%) as dry skin, cutaneous pruritus, contusion and pamnychia, as well as peripheral sensory neuropathy (11.1%). The any-grade events of skin disorders and peripheral sensory neuropathy were mostly observed in all patients. These events were controllable by preventive skin care and by withdrawal and close reduction, respectively. Death due to adverse events was not observed. Adverse events did not require the withdrawal of this regimen. Conclusion: Based on the 18 patients studied, combined therapy with SOX+cetuximab was free of serious adverse events and could he safely administered by reducing the dose or temporarily suspending treatment, as required. These regimens seem to be promising for conversion therapy (4 out of 18 patients) because of good outcomes and an early response.