A 27-year-old Caucasian male with a noncontributory medical history and no previous trauma was referred from the maxillofacial department of the hospital for the endodontic evaluation of the mandibular right first and second molars, which were connected to an extensive asymptomatic osteolytic lesion incidentally discovered on a routine panoramic radiograph and scheduled to be treated surgically under general anesthesia. The patient reported that he had experienced pain and swelling in the right mandible months before, while the first molar had a history of caries, extensive amalgam restoration, and incongruous endodontic treatment performed ten years earlier. The clinical examination showed no sign of buccal or lingual bone expansion, no lymph node involvement, and intact overlaying mucosa. The first mandibular molar was asymptomatic. The right second mandibular molar was asymptomatic with an intact crown, and it responded normally to the sensitivity tests at the time of our examination. The panoramic radiograph showed a well-defined unilocular osteolytic lesion with sclerotic margins located between the two molar teeth and superimposed on the alveolar inferior nerve with a slight displacement of the second molar. The first molar showed inadequate root canal treatment with signs of resorption in the apical third of the distal root involved in the osteolytic lesion. A preoperative periapical radiograph taken using the paralleling technique confirmed these findings (Figure 1). Cone beam computed tomography (CBCT) revealed a well-defined unilocular lesion, with considerable expansion toward the lingual wall and consequent thinning of the lingual plate. From the axial and sagittal sections, it was possible to diagnose a perforation both in the distal and lingual aspects of the apical third of the distal root of the right first molar (Figure 2). To assess the content and vascularity of the lesion, a real-time ultrasound examination with the application of color-power-Doppler (CPD) was performed using a Toshiba Aplio XG (Toshiba Medical Systems, Crawley, UK) apparatus with a regular size, linear, high definition, and multifrequency ultrasound probe at 8-12 MHz. The exam displayed a transonic, fluid-filled lesion with a well-defined hyperechoic bone contour, perilesional vascularity, and no internal vascular supply, suggestive of a cystic lesion (Figure 1). The diagnosis, based on all the exams performed, was a nonendodontic cystic lesion of the right mandible in the area of the first and second mandibular molars and AP in a previously treated first mandibular molar with a perforation in the distal root. The treatment plan was discussed with the patient and comprised the following steps: (1) surgical excision and biopsy of the lesion for the histopathologic evaluation; (2) endodontic retreatment of the right mandibular first molar, with the repair of the perforating defect on the distal root; (3) a possible postsurgical root canal treatment of the second molar. Surgery was performed in the maxillofacial clinic under general anesthesia after an inferior alveolar nerve block together with infiltration with anesthetic of the surrounding tissues. A mucoperiosteal flap was raised exposing the buccal bone, which did not present any sign of resorption or expansion. A bone window was created using a surgical bur with continuous water cooling to reach the lesion (Figure 3); the disclosed bone cavity had the size and shape shown by CBCT and was filled with serum/blood fluid, as seen in the ultrasound exam; thus, a temporary intraoperative diagnosis of TBC was made. The fluid was evacuated, and the walls of the lesion were carefully explored and curetted; however, only a few specimens of tissue were collectable for histopathologic examination. After the formation of the blood clot, the flap was repositioned and sutured. Histologic examination of the tissue fragments reported fibrosclerotic tissue with calcifications and cholesterol clefts, extensively interested in a chronic inflammatory infiltrate with numerous foamy histiocytes and foreign body-like multinucleated giant cells (Figure 3). Four weeks later, the patient was asymptomatic; however, at the postsurgical endodontic assessment, the second molar did not respond to the sensitivity tests, which was due to a possible resection of the alveolar neurovascular bundle, and a diagnosis of pulp necrosis was made. After informed consent was obtained, local anesthesia was administered using mepivacaine 2% 1 : 100 000 epinephrine followed by isolation of the teeth using a rubber dam. Root canal treatment of the second molar was performed in 1 appointment without complications. Two weeks later, the patient was still asymptomatic, and secondary treatment was performed on the first molar. After informed consent, local anesthesia administration, rubber dam isolation, and root canal retreatment of the mesial canals were achieved without obstacles, while the working length determined with the apex locator in the distal root canal was considerably shorter than the length of the root because of perforation, which was established by measuring the CBCT scans. The canals were instrumented manually and irrigated with 5.25% NaOCl and a final rinse of 17% EDTA solution. The apical half of the distal canal was dried with paper points and obturated using Ortho-MTA (BioMTA, Seoul, Republic of Korea) applied with a carrier to seal the perforating defect, while the remaining coronal half was filled with flowable gutta-percha and the tooth restored with composite (Figure 4). Four months later, the patient was asymptomatic, and radiographic control showed an increase in radiopacity and trabeculae formation in the bone (Figure 4). The patient attended the periodical recall visits, and at the five-year follow-up was asymptomatic. The radiographic examination showed complete healing of the lesion, with remineralization of the area around and within the perforated root. An additional CBCT examination depicted the complete formation of the vestibular and lingual cortical plates (Figures 4 and 5).