Background. We have previously described the resection of hypothalamic hamartomas (HH) using a transcallosal approach [Transcallosal resection of hypothalamic hamartomas, with control of seizures, in children with gelastic epilepsy, Neurosurgery, 2001]. Since then, we have refined the technique and now describe in detail an anterior transcallosal transseptal interforniceal approach to the third ventricle as a variation of the standard transcallosal interforniceal approach. The results of this series are presented to demonstrate the safety and efficacy of this approach. Method. HH were resected via an anterior transcallosal, transseptal, interforniceal approach to the third ventricle. This is a more anterior approach to the third ventricle with a more acute trajectory than has been described previously. Results. This approach provided excellent access to the floor of the third ventricle with minimal forniceal retraction and avoidance of dissection of the deep venous structures. Transcallosal resection of HH was performed in 45 patients aged 2.9-33 years (mean 11.3 years). Morbidity was minimal, including transient hemiparesis in 3, ongoing diabetes insipidus in 2, early short-term memory impairment in 16 (persistent in 6) and one patient developed pneumonia postoperatively but recovered. Conclusion. The anterior transcallosal transseptal interforniceal technique is an effective and relatively safe technique when used for the resection of HH. This operative approach is applicable to other pathology in the third ventricle or hypothalamic region and has advantages compared with the standard transcallosal approach to the third ventricle.