We report the case of a toddler, with a history of mild atopic dermatitis (AD) since early infancy, presented to the Giannina Gaslini, a pediatric polyclinic hospital, 14 days after measles-mumps-rubella (MMR) vaccination, for the occurrence of a disseminated vesico-pustular rash, accompanied by general malaise, fever, restlessness, and anorexia. Eczema herpeticum (EH) was diagnosed clinically and confirmed by laboratory examinations. The exact pathogenesis of EH in AD is still debated and possibly involves an inter-play between altered cell-mediated and humoral immunity, failure to up-regulate antiviral proteins, and exposure of viral binding sites through the dermatitis and an epidermal barrier failure. We hypothesize that in this particular case, MMR vaccination might have played an additional important role in the alteration of innate immune response, facilitating the manifestation of herpes simplex virus type 1 in the form of EH.