Background: We determined whether serum levels of Receptor Activator for Nuclear Factor κ B Ligand (RANKL), Osteoprotegerin (OPG), and the RANKL/OPG ratio could be useful biomarkers for the severity of oral lesions in bisphosphonate-related osteonecrosis of the jaw (BRONJ). Material and Methods: A case-control study in which Group 1 consisted of 41 patients with BRONJ due to intravenous bisphosphonates, and Group 2 consisted of 44 healthy control cases. The plasma levels of RANKL and OPG were analyzed by an ELISA assay. The OPG/RANKL ratio was also calculated. We determined if the mean serum values differed among the different stages of BRONJ. Results: Serum levels of RANKL were lower in Group 1 than in Group 2 (p =0.01), and serum levels of OPG were higher in patients with BRONJ than in the controls (p =0.006). The ratio of RANKL/OPG was greater in the controls than in Group 1 (P >0.01). There were no significant differences in the serum levels of RANKL and OPG among the different stages of osteonecrosis (P > 0.05). Conclusions: Serum levels of RANKL and OPG, and the RANKL/OPG ratio were not valuable biomarkers for determining the severity of oral lesions in patients with BRONJ. Key words:Bisphosphonates, RANKL, OPG, Osteonecrosis.