Posttransplant lymphoproliferative disorder is a group of heterogenous disorders that occur after solid-organ transplant. The overall incidence is between 1% and 20%. In orthotopic liver transplant recipients, the reported incidence ranges from 2% to 10%, while the incidence is greater in children (9.7%-11%) and lesser in adults (1.7%-3%). The following treatment options are considered for patients with posttransplant lymphoproliferative disorder: reduction of immunosuppression, single-agent rituximab, rituximab and chemotherapy, surgery and radiation, antivirals targeted at the Epstein-Barr virus, and cytotoxic T-lymphocytes targeting the Epstein-Barr virus. This report describes a 61-year-old man who presented after an orthotopic liver transplant with a large periportal soft tissue mass that was shown on biopsy to be a monomorphic, CD20+, diffuse, large B-cell lymphoma, nongerminal center type. He was treated with reduced immunosuppression, followed by single-agent rituximab, then with an anthracycline-based chemotherapy regimen: rituximab, etoposide, prednisone, vincristine, doxorubicin, and then a platinum-based salvage chemotherapy with rituximab, dexamethasone, cytarabine, and cisplatin with a good response.