Posttransplant lymphoproliferative disorders are severe complications that arise after solid organ transplantation, which are often related to Epstein- Barr virus. Reports are anecdotal, and a standardized therapy does not exist. We report a case of a 36-year-old man who developed posttransplant lymphoproliferative disorder of the oropharynx 1 year after receiving a heart transplant. A short review of the literature is presented, after which a new therapeutic approach that combines antiviral therapy, monoclonal antibodies, and a sirolimus-based maintenance immunosuppression regimen with reduced target trough levels of tacrolimus is introduced. The patient achieved complete remission and was free from recurrence 18 months after the therapy was initiated.