The report of anesthetic technique failure is crucial and the etiology of the problem should be determined. We describe a case of locoregional anesthesia failure, in which, after excluding its most common causes, the resistance to local anesthetics was considered as the most probable clinical hypothesis. For this reason, a genetic test was performed, as well as the efficacy of other local anesthetics was evaluated, constituting a different approach in the cases of locoregional anesthesia failure. True resistance to local anesthetics is difficult to diagnose so information about this is scarce in the literature. One of the proposed causes is a mutation of sodium channels where local anesthetics bind. If not recognized, the application of locorregional anesthesia in this patient's condition can lead to unpleasant experiences and unnecessary risks, related to toxic levels of local anesthetics. For this reason, the resistance to local anesthetics should be always precluded in cases of strong clinical suspicion. This approach could be applied in similar cases.