Accurate diagnosis and identification of relevant etiologic factors are pivotal for effectively managing endodontic-periodontal lesions. Once a diagnosis is established, the therapy focuses on eliminating the primary cause, followed by a subsequent diagnostic phase after healing. The definitive understanding of the diagnosis and etiology of endodontic-periodontal lesions often becomes clear in retrospect, based on the outcomes of the therapy. When probing acute periodontal lesions, deep probing depths may occur without permanent loss of periodontal attachment. If the acute lesion was not induced by a periodontal cause and if no periodontal etiology arises secondarily, resolving the primary cause of the endoperiodontal lesion can lead to the spontaneous resolution of the pocketing. This results in spontaneous healing of periodontium without the need for intentional periodontal therapy. A clinical dilemma arises when considering periodontal treatment during the acute inflammatory phase of endo-periodontal pathology. It is advisable to refrain from mechanical root instrumentation particularly if a clear periodontal cause is not apparent, to prevent from iatrogenic damage to periodontal fibers and the potential risk of gingival recessions. However, this does not imply avoiding periodontal therapy entirely for every case. Rather, it is recommended to delay the decision on root instrumentation until a new diagnostic phase is conducted following the healing of the endodontic etiology.