Many systemic diseases have oral and/or pharyngeal manifestations. Mucosal lesions in the upper aerodigestive tract may be caused by granulomatous inflammations, and infectious, autoimmune and neoplastic diseases before they appear systemically or otherwise. ENT specialists can play a decisive role in identifying patients with pathological mucosal changes and transfer them to dermatology, hematology, gastroenterology or maxillofacial surgery in order to assure the best possible treatment. This article presents the case of an elderly female patient with a history of necrotising severe stomatitis that turned out to be a rare B-cell lymphoma. In the second part of the article, we present a number of common and rare diseases that may be encountered in ENT practice with an overview of clinical manifestations and current diagnostic modalities.