Primary T-cell CNS lymphoma is a rare and aggressive malignancy. High-dose methotrexate (MTX) based chemotherapy regimens are used as standard first-line treatment, followed by consolidative strategies to improve the duration of response. Although MTX-based therapy has been shown to be efficacious, treatment options for MTX-refractory disease are not well-defined. Here, we report a case of a 38-year-old man with refractory primary T-cell CNS lymphoma who demonstrated a complete response to pemetrexed treatment. He subsequently received conditioning chemotherapy consisting of thiotepa, busulfan and cyclophosphamide followed by autologous stem cell transplantation. The patient continues to remain recurrence-free to date at 9 years post-treatment.