OBJECTIVES: Traditionally, healing after surgical endodontic retreatment (SER); i.e. apicectomy with or without a retrograde filling, is assessed in periapical radiographs (PR). Recently, the use of cone beam CT (CBCT) has increased within endodontics. Generally, CBCT detects more periapical lesions than PR, but basic research on the true nature of these lesions is missing. The objective was to assess the diagnostic validity of PR and CBCT for determining inflammation in SER cases that were re-operated (SER-R) due to unsuccessful healing, using histology of the periapical lesion as reference for inflammation. METHODS: Records from 149 patients, receiving SER 2004-10, were screened. In total 108 patients (119 teeth) were recalled for clinical follow-up examination, PR and CBCT, of which 74 patients (83 teeth) participated. Three observers assessed PR and CBCT as "successful healing" or "unsuccessful healing" using Rud and Molven's criteria. SER-R was offered to all non-healed teeth with expected favourable prognosis for subsequent functional retention. During SER-R, biopsy was performed and histopathology verified whether or not inflammation was present. RESULTS: All re-operated cases were assessed non-healed in CBCT while 11 of these were assessed successfully healed in PR. Nineteen biopsies were examined. Histopathologic diagnosis revealed 42% (teeth = 8) without periapical inflammation, 16% (teeth = 3) with mild inflammation and 42% (teeth = 8) with moderate to intense inflammation. A correct diagnosis was obtained in 58% with CBCT (true positives) and 63% with PR (true positives+true negatives). CONCLUSIONS: Of the re-operated teeth, 42% had no periapical inflammatory lesion, and hence no benefit from SER-R. Not all lesions observed in CBCT represented periapical inflammatory lesions.