The late failure of endoscopic third ventriculostomies (ETVs) has been described as a consequence of scarring phenomena involving the third ventricular floor. Although the possibility of closure of the stoma by intraventricular tumor seeding has been hypothesized, no case of ETV failure caused by tumor diffusion has been reported in the literature. The authors report on a 19-year-old patient, affected by obstructive hydrocephalus associated with a periaqueductal pilocytic astrocytoma, who underwent late secondary lesional obstruction of an ETV performed at diagnosis. The authors suggest tumor extension along the diencephalic neural pathways as the possible cause of ETV failure in this patient.