Abstract Introduction. The concomitant existence of combined endodontic-periodontal lesions is a clinical dilemma that can compromise diagnosis, prognosis and treatment planning. Understanding the biology of both lesions on severely compromised teeth can determine the approach to therapy for a successful regenerative treatment outcome. Objective of the study. The aim of this analysis was to evaluate the effectiveness of endodontic treatment with subsequent regenerative periodontal therapy in treating advanced endo-perio lesions. Materials and methods. One patient with grade III endoperiodontal lesion was selected for clinical case presentation. Clinical and radiographic (CBCT) evaluation yielded to an accurate diagnosis. A combined endodontic and periodontal surgical regenerative approach was performed. Results. At follow-up appointment after 6 months, clinical and radiographic evaluation showed partial healing of the soft tissue and bone lesion with probing depth reduction, significant bone and clinical attachment gain.Probing depth was ≤ 3mm, from 10 mm to 2 mm. Clinical attachment level improved from 10 mm to 5 mm. Radiographic analysis showed a radiographic bone level gain of 3 mm. Conclusion. The success of the treatment depends on the correct application of the steps in the treatment of endoperiodontal lesions, as well as on the patient’s compliance with rigorous post-treatment hygiene. Regenerative periodontal therapy in combination with proper endodontic treatment are a viable option for saving teeth with advanced endo-perio lesions. Key words: endo-periodontal lesion, periodontitis, pulpitis, diagnosis, treatment.