We report a case of a 3.5-year-old female with a very high copy number of human herpesvirus 6 (HHV-6) detected by PCR in blood during acute lymphoblastic leukemia induction therapy. The patient was unsuccessfully treated with antiviral drugs. HHV-6 genome was shown to be constitutively integrated into chromosome 22q-tel, likely to be inherited from the mother who was found to carry high HHV-6 copy number. This case highlights the importance of excluding HHV-6 chromosomal integration before diagnosing HHV-6 infection or reactivation in immunocompromised patients.