There is a paucity of literature addressing the management of methotrexate (MTX) hypersensitivity. We developed a high-dose MTX readministration protocol based on a modified, prolonged carboplatin desensitization protocol. Over 1.5 hours, 1/1000 of the total intravenous dose was administered followed by 1/100 over 1.5 hours, 1/10 over 6 hours, and the rest of the full dose over 24 hours. MTX readministration was successfully tolerated on three occasions in a 17-year-old male patient with T-cell acute lymphoblastic lymphoma and a history of urticarial reactions to MTX. This high-dose MTX readministration protocol may be valuable for treating patients with T-cell acute lymphoblastic lymphoma and suspected immediate MTX hypersensitivity.