Introduction: Both Actinomyces and Nocardia are Gram-positive microbes characterized by a filamentous morphology. Both can be causative agents in slowly progressive, localized, or disseminated infections that are rare and typically occur in immunocompromised patients. Oral infections involving both microorganisms are very rare. Case Presentation:A black male with a history of Type 2 diabetes was referred with a chief complaint of a persistent 3 mm × 3 mm swelling facial to the mandibular central incisors. The swelling was asymptomatic except for occasional discharge of purulent exudate. Examination revealed 5-to 6-mm mesio-lingual and mid-lingual probing depths. Radiographs revealed a well-defined radiolucency between the roots of teeth #24 and #25. A full-thickness gingival flap was reflected exposing an oval-shaped bony defect, which was debrided and the contents submitted for microscopic examination. The resulting defect was filled with demineralized freeze-dried bone allograft (DFDBA) and capped with calcium sulfate. The patient was prescribed amoxicillin and 0.12% chlorhexidine gluconate mouthrinse. Examination of the biopsied tissue revealed both Actinomyces and Nocardia microorganisms. The patient was followed for 24 months and remains symptom-free with noted radiographic evidence of bone fill in the lesion area. Conclusions:This may be the first published report of an oral infection featuring both Actinomyces and Nocardia.The case reinforces the importance of microscopic examination of biopsy material removed from unusual and persistent pathologic lesions that are destructive of bone. Clin Adv Periodontics 2018;8:167-172.