The pathogenesis of Medication-Related Osteonecrosis of the Jaw (MRONJ) is not fully understood, however, surgical trauma is thought to play a role. Therefore, the aim of the current pilot study was to compare the incidence and characteristics of MRONJ following single or multiple molar tooth extractions in a rat model. To this aim, twenty male Lewis rats were treated with subcutaneous injection of zolendronic acid (ZA), an established bone anti-resorption agent, (7.5 $\mu $g/kg) and dexamethasone (Dex), (1 mg/kg), or saline, once a week, for 11 weeks. At three weeks, the first or both first and second maxillary molar teeth were extracted. Eight weeks following extraction, rats were sacrificed and extraction sites were evaluated. Clinical macroscopic examination showed MRONJ-like lesions in all single extraction ZA/Dex-treated rats, showing exposed bone. In the control and multiple extraction ZA/Dex-treated groups, none of the rats showed visible signs of MRONJ. Histological characteristics of MRONJ were found in all ZA/Dex-treated rats (both single and multiple extractions), whereas rats treated with saline showed almost no empty lacunae and necrotic bone. In conclusion, the extent of the surgical field may not be the key factor in MRONJ development since only rats with single tooth extraction displayed exposed bone. However, histological characteristics were identified in both models. Therefore, preclinical studies that aim to evaluate histological features of MRONJ may use both models, whereas when a clinically exposed bone is required, the single tooth extraction model appears to be preferable. Further large scale studies are warranted to corroborate the present findings.