We report that a case of maxillary sinus carcinoma with severe pain for radiation oral mucositis was successfully managed by using indomethacin spray. Fifty three-year-old male who was treated with radiation and chemotherapy including 5-FU for his maxillary sinus carcinoma developed oral mucositis with severe pain. Several medications such as diclofenac sodium (tablet), oxycodone hydrochloride (sustained-release tablet), morphine sulfate (fine granule), fentanyl (patch), azulene (gargle) and lidocaine (viscous) did not provide satisfactory effects on the pain control. We, therefore, tried to use indomethacin spray (0.2 mg/0.08 mL/push) with the daily dose of 9.6±5.2 mg (2-10 push/once, 1-11 times daily). Indomethacin spray provided dramatic effects on his pain relief with the significant reduction of pain score (face scale) from 2.4±0.4 to 1.0±0.1 (p<0.01). Mean time for pain relief was 8.7±2.2 min. after applying indomethacin spray. The effects of indomethacin spray on the radiation oral mucositis were evaluated by pain score in five patients with head-and-neck carcinoma. The pain score was improved in all cases after introducing indomethacin spray (before vs. after: 3.2±0.5 vs. 1.6±0.6, p<0.01) with the 8.1±3.8 mg/day. There was no adverse events associated with the use of indomethacin spray. The results suggest that the use of indomethacin spray is an alternative approach to control the pain for radiation oral mucositis in patients under radiation therapy for head-and-neck carcinoma.