Pallister-Hall syndrome (PHS) is a very rare syndrome characterized by hypothalamic hamartoma (HH), polydactyly, panhypopituitarism, imperforate anus and other visceral anomalies. Contrary to patients with isolated HH, neurological dysfunction and precocious puberty are uncommon and seizures are usually well controlled with anticonvulsant medication. Therefore, conservative management of HH is advised. To the best of our knowledge, seven cases of PHS with surgical resection of the HH have so far been reported. Five patients were either seizure-free or had >90% seizure reduction postoperatively. Here, we present a case of PHS of a patient who also underwent transcallosal endoscopic resection of the HH with a subsequent 70% reduction in seizure frequency.