We identified a stem cell donor with chromosomally integrated human herpesvirus (HHV)-6 and monitored the recipient for HHV-6 after transplantation. The appearance and subsequent increase in HHV-6 load paralleled engraftment and an increase in white blood cell count. Fluorescent in situ hybridization analysis showed integrated HHV-6 on chromosome band 17p13.3 in the donor and in the recipient after transplantation but not in the recipient before transplantation. The increase in viral load due to the genetic transmission of integrated HHV-6 could have been misinterpreted as substantial active infection and, thus, led to the administration of toxic antiviral therapy. We suggest that the confounding influence of integration be considered in laboratory investigations associating HHV-6 with disease.