Systemic sclerosis is a chronic, progressive disease with an extremely poor prognosis. The incidence of malignant tumors in patients with systemic sclerosis is increased when compared with that of the general population. In certain malignancies, systemic sclerosis presents as a paraneoplastic process. The symptoms of sclerosis in the organs of the head and neck often overlap with symptoms of malignant diseases, which may increase the difficulty of a differential diagnosis. Additionally, the presence of sclerosis may complicate standard examination procedures, due to poor access to the oral cavity and oropharynx. When considering treatment options, it is important to evaluate the surgical and oncological risks to soft tissues of the head and neck with regard to both diseases, as well as the relatively poor prognosis for systemic sclerosis and oropharyngeal cancer. The low incidence of patients with systemic sclerosis and oropharyngeal carcinoma together presents a clear case for a casuistic approach. Based upon our own experience, we can attest to the difficulty of treating such patients. However, we have no evidence to indicate that these patients have reduced tolerance to surgical treatments. The current study presents the case of a 47-year-old female with systemic sclerosis, who was diagnosed with oropharyngeal carcinoma. The patient initially tolerated radiotherapy treatment well, however post-radiotherapy complications occurred. Despite many enigmatic indications to the contrary, it appears that the complications in this instance may be due to late toxicity from radiotherapy.