•Rituximab has been frequently utilized for the treatment of a wide range of neurologic diseases including 'Devic's syndrome.•Previous case reports have described cases of osteonecrosis, retinal and nasal skin necrosis.•This case report addresses a patient with 'Devic's syndrome presented with palatal mucosal necrosis after rituximab treatment.•Due to the increasing administration of rituximab, awareness about mucosal necrosis should be raised. Rituximab is a B-cell-depleting unconjugated monoclonal IgG1 antibody that targets the transmembrane protein CD20. This article reports on a case with the rare complication known as Rituximab-associated mucosal necrosis. The present case report addresses, for the first time, a patient affected by Devic's syndrome presenting with oral manifestations of palatal necrosis after rituximab treatment. The present case raises the possibility of anti-CD20 antibody contributing to the development of palatal mucosal necrosis in some patients. Given the increasing administration of rituximab as a result of its efficacy against several diseases, a report on the potential iatrogenic effects of this drug is essential.