Purpose: A fully digital approach to oral prosthodontic rehabilitation requires the possibility of combining (i.e., registering) digital documentation from different sources. This becomes more complex in an edentulous jaw, as fixed dental markers to perform reliable registration are lacking. This validation study aimed to evaluate the reproducibility of 1) intraoral scanning and 2) soft tissue-based registration of an intraoral scan with a cone-beam computed tomography (CBCT) scan for a fully edentulous upper jaw. Materials and Methods: Two observers independently performed intraoral scans of the upper jaw in 14 fully edentulous patients. The palatal vault of both surface models was aligned, and the inter-observer variability was assessed by calculating the mean inter-surface distance at the level of the alveolar crest. Additionally, a CBCT scan of all patients was obtained and a soft tissue surface model was generated using patient-specific gray values. This CBCT soft tissue model was registered with the intraoral scans of both observers, and the intraclass correlation coefficient (ICC) was calculated to evaluate the reproducibility of the registration method. Results: The mean inter-observer deviation when performing an intraoral scan of the fully edentulous upper jaw was 0.10 ± 0.09 mm. The inter-observer agreement for the soft tissue-based registration method was excellent (ICC=0.94; 95% confidence interval, 0.81–0.98). Conclusion Even when teeth are lacking, intraoral scanning of the jaw and soft tissue-based registration of an intraoral scan with a CBCT scan can be performed with a high degree of precision.