Apical periodontitis and vertical root fracture (VRF) might coexist in the same root, thus representing a di-agnostic challenge in endodontics. Diagnosis should be based on detailed clinical examination and precise radiographic interpretation in addition to histological examination, if needed. The histological findings of the case presented showed the possible coexistence of a VRF in the coronal third of the root and signs of apical periodontitis caused by intracanal infection in the apical third of the same root. The presentation of this case underlines the importance of histological examination as a valid complementary diagnostic tool with clinical and radiographic examinations in reaching an accurate diagnosis once the root has been extracted.