We report herein our institutional experience in the treatment of diffuse intrinsic pontine glioma (DIPG) with a hypofractionated external-beam radiotherapy schedule. Between April 1996 and January 2004, 22 patients (age 2.9-12.5years) with newly diagnosed DIPG were treated by hypofractionated radiation therapy delivering a total dose of 45Gy in daily fractions of 3Gy, given over 3weeks. No other treatment was applied concomitantly. Fourteen of the 22 patients received the prescribed dose of 45Gy in 15 fractions of 3Gy, and 2 patients received a total dose of 60 and 45Gy with a combination of two different beams (photons and neutrons). In five cases the daily fraction was modified to 2Gy due to intolerance, and one patient died due to serious intracranial hypertension after two fractions of 3Gy and one of 2Gy. Among 22 children, 14 patients showed clinical improvement, usually starting in the second week of treatment. No grade3 or 4 acute toxicity from radiotherapy was observed. No treatment interruption was needed. In six patients, steroids could be discontinued within 1month after the end of radiotherapy. Median time to progression and median overall survival were 5.7months and 7.6months, respectively. External radiotherapy with a radical hypofractionated regimen is feasible and well tolerated in children with newly diagnosed DIPG. However, this regimen does not seem to change overall survival in this setting. It could represent a short-duration alternative to more protracted regimens.