Since Medication-Related Osteonecrosis of the Jaw (MRONJ) is challenging to treat, prevention and early detection are fundamental to limit progression. While some imaging techniques such as computed tomography (CT) scans are helpful to estimate the extent of osteonecrosis in clinically evident MRONJ, methods for early detection and identification of patients at risk for MRONJ need further investigations. The aim of our retrospective study was to evaluate the role of bone scintigraphy (BS) in the early prediction of MRONJ. BS of patients treated with antiangiogenic or antiresorptive therapy for bone metastases were evaluated for pathological tracer uptake of the jaws. Sensitivity, specificity, predictive values of BS for the prediction of MRONJ were investigated. Moreover, the latency from the first presence of pathological tracer uptake in BS to clinically evident MRONJ was determined. The significance of pathologic BS for MRONJ detection was calculated by Fisher’s exact test and the odds ratio was determined. A total of 19 patients with representative BS were recruited from our Department database. Whole body BS in anterior and posterior positions were reviewed by a specialist in nuclear medicine, blinded to MRONJ diagnosis, for pathological tracer uptake of the jaws. Results were compared to development of clinically evident MRONJ. Sensitivity and specificity of BS for MRONJ prediction were respectively 90% and 82%. Positive and negative predictive values were 64% and 96%, respectively. Median time from the first presence of pathological tracer uptake in BS to clinically evident MRONJ was 20.3 months (range 7–41). Pathologic findings on BS were significantly (p < 0.001) more often observed in patients who developed MRONJ compared to patients who did not. The risk to develop MRONJ was 41.4-fold increased when BS was pathologic. According to our results, BS is an accurate method for the prediction of MRONJ.