Allogeneic peripheral blood stem cell transplantation (allo PBSCT) is a recognized treatment modality for hematological malignancies resistant to conventional chemoradiotherapy. The post-transplant immune-mediated graft-versus-leukemia effect has major curative potential. In this case presentation, the allogeneic approach to resistant recurrent primary central nervous system (CNS) lymphoma using peripheral blood stem cells from an HLA identical sibling after immuno-suppressive non-myeloablative conditioning, was examined clinically. The patient in question had relapsing refractory primary CNS lymphoma and is the first to be treated with this modality. She developed early skin and liver-localized grade II graft-versus-host disease after allo PBSCT, which then responded to short-term treatment. Chimeric studies at the time showed 100% donor cells and repeated magnetic resonance imaging of the brain revealed gradual shrinkage of the tumor. Three months after transplant the cerebral mass was no longer evident and currently, 30 months after transplantation, the patient continues to be disease free. The absence of any signs of malignancy suggests the development of a durable graft-versus-lymphoma effect in this brain tumor and indicates that this effect may be achieved even after non-myeloablative conditioning.