We describe a rare case of diffuse leptomeningeal oligodendrogliomatosis associated with the human herpes virus 6 variant A (HHV-6 A). A 2-year-old boy presented with progressive neurological symptoms and hydrocephalus. The patient had a VP shunt placement but did not fully recover. HHV-6 A was detected in both CSF and serum by nested PCR. His symptoms improved repeatedly, but temporarily, on antiviral treatment. An open brain biopsy, ten months after presentation, revealed leptomeningeal tumour as well as the presence of viral DNA in the tumour tissue. The role of HHV-6 A could be that of a reactivated opportunist. However, this case also raises the question whether this neurotropic virus, with malignant transforming properties in vitro, may have a role in pathogenesis in some cases of brain malignancy.