Hydroa vacciniforme is a rare, usually quite severe, photo-dermatosis. Association with Epstein-Barr virus infection and a possibly increased risk of lymphoproliferative malignancy have been demonstrated. We describe here four patients with Epstein-Barr virus-associated hydroa vacciniforme treated with acyclovir/valacyclovir therapy with a good clinical response. The children were reported to have less fatigue, fewer eruptions, less scarring, and increased ability to spend time outdoors without provoking new eruptions. This was also in agreement with clinical observations. However, one patient progressed into an anaplastic lymphoma kinase-1-negative anaplastic large-cell lymphoma in the upper jaw. This was preceded by an increase in EBV viral load. Acyclovir/valacyclovir therapy is a safe treatment. Further studies are required to confirm these results.