This is an 8-year follow-up to the author’s initial report of a randomized phase II study in patients with newly diagnosed primary CNS lymphoma treated with high-dose methotrexate-based induction chemotherapy followed by whole-brain radiotherapy (WBRT) or high-dose chemotherapy (thiotepa-busulfan-cyclophosphamide) with autologous stem-cell transplantation (ASCT). They conclude that 40 Gy WBRT should be avoided in first-line treatment in this population because of its neurotoxicity and suboptimal efficacy in reducing relapses, while ASCT appears to be highly efficient in preventing relapses.