Craniopharyngiomas are benign intracranial tumors located in the sellar and suprasellar region. Their size and extent of invasion into surrounding structures vary considerably. While the majority of craniopharyngiomas on presentation are between 1–3 cm without hypothalamic invasion, a significant proportion of patients present with ‘giant’ craniopharyngiomas of >4cm in dimension with large cystic extension through the 3rd ventricle. These tumors pose a challenge both for surgical resection as well as for radiation therapy. Proton beam therapy (PBT) has become the preferred standard of care after subtotal resection of pediatric craniopharyngiomas. In the setting of giant craniopharyngioma, the use of proton therapy allows a reduction of dose to surrounding normal brain, but changes in cyst volume can result in either under-coverage of tumor or excess dose to surrounding brain, an effect further magnified by the sharp gradients associated with proton dose distributions. In this case report we describe the proton treatment planning and intra-treatment monitoring of two patients with giant craniopharyngiomas with largest pre-operative of dimension 6cm, and 9cm, respectively, and 6cm and 5.5cm, respectively, pre-radiation. Both patients had drains inserted to Ommaya reservoirs. We performed surveillance imaging during RT utilizing spiral computer tomography (CT) on a weekly basis and reconstructed the treatment dose on the surveillance CTs to ensure target coverage and normal tissue sparing. We compared the dosimetry in these cases for PBT versus intensity-modulated radiation therapy, characterized the cyst evolution during treatment in 3 dimensions, and define an optimized protocol for treatment planning and intra-treatment monitoring.