BACKGROUND: Bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) is an unpredictable, debilitating adverse effect. Recently, genetic polymorphisms have arisen as promising tools to identify patients with a higher risk of drug-related adverse events. AIM: We aimed to examine the association between the aromatase polymorphism g.132810C>T, and the estrogen receptor polymorphisms g.156705T>C and g.156751A>G, and the risk of BP-related ONJ. METHODS: Eighty-three subjects were included in the study. A clinical and radiological examination was conducted on oncologic subjects treated with zoledronic acid. Subjects with histologically confirmed ONJ were included in the test group (n = 30) whereas subjects with good oral health were included in control group (n = 53). Aromatase and estrogen receptor polymorphisms from blood samples were analyzed. RESULTS: The aromatase g.132810C>T polymorphism displayed an over-representation of the TT genotype in the test group (36.67 vs 16.98%; p < 0.05). There was no significant difference in either estrogen receptor polymorphism genotype frequency between the test and control groups. CONCLUSION: Our data suggest a role for the g.132810C>T polymorphism in predicting ONJ risk. These results can pave the way to the personalization of BP therapy, based on individual genotype.