Plasma cell mucositis (PCM) is a rare plasma cell proliferative disorder of the upper aerodigestive tract with an unknown etiology. Including the present case, only 22 cases have been reported in the English-language literature. PCM affects adult patients at an average age of 56.6 years. Clinical features are an intensely erythematous mucosa with papillomatous, cobblestone, nodular, or velvety surface changes. Symptoms include oral pain of long duration, dysphagia, persistent hoarseness, and pharyngitis. The majority of cases have a history of autoimmune or immunologically mediated disease. The histopathologic features of a dense, submucosal plasma cell infiltrate are not specific and must be differentiated from other reactive and neoplastic conditions. Diagnosis of PCM depends on clinical pathologic correlations. The present case was complicated by evidence of a monoclonal plasma cell population. The significance of this case is the differentiation of a benign disease from one that is potentially life threatening.