Background: Impulsive aggression is the core symptom of intermittent explosive disorder, which can be a feature of several psychiatric disorders. There is a subset of individuals who do not respond adequately to medical treatment; they are treatment refractory. The objective of this report is to describe a case of a patient with a background of schizophrenia and concomitant refractory aggressiveness disorder, treated with two-stage bilateral hypothalamotomy and unilateral amygdalotomy with Gamma Knife radiosurgery (GKR). Case Description: A 36-year-old male presented with a background of paranoid schizophrenia. Episodes of self- and hetero-aggressiveness were present at the initial diagnosis. High dosages of psychotropic medication were taken, and 70 sessions of electroconvulsive therapy were performed; however, no adequate response was obtained. Bilateral hypothalamotomy plus left amygdalotomy through GKR was performed. After 25 months of follow-up, a marked decrease in the frequency, degree, severity of aggressiveness and the requirement for psychotropic medications was observed. Conclusion: Hypothalamotomy plus amygdalotomy with Gamma Knife may be an effective ablative technique for the management of refractory aggressive disorder in patients with mental illness.