Aim To determine whether the outcome of cone beam computed tomography (CBCT) examinations performed in accordance with the European Commission guidelines in a clinical setting has an impact on choosing diagnoses in endodontics. Methodology A prospective observational study was conducted. Fifty-three consecutive patients (81 teeth) from two different endodontic specialist clinics in Sweden were followed. After performing a thorough clinical examination (based on the history, clinical findings, and diagnostic tests such as intra-oral radiography), the examiner wrote down a preliminary diagnosis before CBCT examination. After the CBCT examination, a new diagnosis was made by the same examiner. Both the pre- and the post-CBCT examination diagnoses were plotted according to patients and teeth. The CBCT examinations were performed using similar equipment and protocols that were standardized amongst the clinics. Results The diagnoses were changed for at least one tooth in 22 patients (41%); overall, the diagnoses were changed for 28 teeth (35%). Conclusion CBCT has a substantial impact on diagnostic thinking in endodontics when used in accordance with the European Commission guidelines.