Ketamine oral rinse provided effective palliation of intractable mucositis pain in a 32-year-old woman with squamous carcinoma of the tongue undergoing radiation therapy. Pain at rest and with eating decreased with ketamine, allowing for a tapering of her opiate dose. No side effects of ketamine were reported. Treatment benefits most likely arose from the inhibition by ketamine of peripheral N-methyl D-aspartate receptors, though other mechanisms of action may have been contributory. Further evaluation of topical ketamine in the treatment of mucositis-related pain, and, potentially, other causes of inflammatory oral pain, are warranted.