Purpose: The purpose of the study was to investigate how cancer patients with maxillofacial defects evaluate their quality of life after prosthodontic therapy, complemented by a retrospective interview for judging the various therapy steps. The results were compared with a nontumor control group (multiple tooth extractions) and with population-based norm data. Materials and Methods: A total of 34 patients were included in the study, 17 in each group. Patients first filled in a questionnaire and then answered additional questions in a standardized interview. Results: At the time of investigation, tumor patients did not significantly differ from nontumor patients regarding global quality of life. However, tumor patients had significantly less favorable values regarding role functioning, speech, mouth opening, and dry mouth, as well as pain and swallowing. In comparison with the reference data of the German population, tumor patients had considerable deficits (> 20 points) regarding role functioning, dyspnea, and financial difficulties. Other deficits (> 10 points) became apparent in global quality of life, fatigue, insomnia, and appetite. When reflecting the course of disease and recovery, tumor patients rated the diagnosis as the most stressful event and reported that the family was most instrumental in the recovery process. Conclusion: Patients with maxillofacial defects after treatment for malignancy suffer from numerous clearly definable quality of life-related symptoms and problems, even after prosthodontic treatment. These patients need psychologic care at the time of diagnosis to alleviate the burden of the cancer diagnosis and prepare for the demanding treatment. After completion of the prosthodontic treatment, therapy options for pain or speech problems should be offered.