Enterovirus meningoencephalitis is rare but can be severe. Very few cases of these infections have been reported in pediatric oncology. We report the case of a 10-year-old boy with tibial osteosarcoma and lung metastases who developed enterovirus 71 meningoencephalitis during aplasia. Clinical features comprised fever, hypotension, vesicular rash, generalized seizures, and altered consciousness. Diagnosis was confirmed by polymerase chain reaction on samples of cerebrospinal fluid and skin vesicles. The patient received treatment with intravenous immunoglobulins with an excellent outcome with no cutaneous or neurologic sequelae. Immunoglobulin therapy could be considered in cases of invasive enteroviral infection with such severity in pediatric oncology.