Abstract Methotrexate is a vital medication in treating different types of malignancies. There are few reports of successful administration of intravenous methotrexate post adverse reaction by step-up desensitization. We share here, our experience in overcoming methotrexate hypersensitivity though administration of methotrexate by fixed rate infusion in an allergic child who failed a step-up methotrexate desensitization protocol. The outcome of this case suggests an underlying, non IgE mediated mechanism for the adverse reaction.