Medication-Related Osteonecrosis of the Jaws (MRONJ) is a difficult-to-treat complication of the therapy of osteoporosis and some malignancies cured with bisphosphonates and antiresorptive drugs. The pathomechanism is unclear, but there is increasing observation that Actinomyces infection may play a role in its development and progression. The aim of our study was to demonstrate that histological examination using a validated triple staining procedure for Actinomyces bacteria strains can detect a high rate of Actinomyces infection in patient's samples with MRONJ. 112 previously hematoxylin-eosin (HE) stained samples submitted with the clinical diagnosis of MRONJ were re-evaluated histologically using an appropriate triple special staining validated for the identification of Actinomyces infection. During the first evaluation, when pathologists did not specifically look for Actinomyces, only 8.93% of the samples were reported as positive. In contrast, re-evaluation with triple staining provided a yield of 93.7% positive samples, therefore, we suggest the triple special staining to be standard in MRONJ histology evaluation. These results show that if the clinician suspects Actinomyces infection and brings this to the attention of the pathologist, it could significantly increase the number of correct diagnoses. It serves as an aid for clinicians in therapeutic success of MRONJ by selecting a long-term adequate antibiotic medication which is suitable for the elimination of actinomyces infection.