A hematopoietic stem cell transplant recipient developed a mucosal herpes simplex virus-1 (HSV-1) infection while under acyclovir (ACV) treatment (HSV was later shown to be resistant to ACV). Concomitantly, the patient presented a hemorrhagic cystitis (HC) due to polyomavirus BK, for which intravenous cidofovir (CDV) was prescribed. The patient benefited from the broad-spectrum anti-DNA virus activity of CDV, and not only the HC resolved without signs of nephrotoxicity but also the HSV-1 lesions disappeared. This is the first report describing the effect of CDV on 2 simultaneous and unrelated DNA viral infections in an immunosuppressed transplant recipient. In addition, we describe here that this HSV-1 isolate possesses a unique phenotype and genotype.