Increasing numbers of patients have received autologous stem cell transplants (ASCT) for hematologic malignancies. Since only a fraction of these patients are cured, physicians are more frequently faced with the dilemma of how to manage relapse post-transplant. Potential advantages of allogeneic transplantation (alloBMT) over ASCT include lack of graft tumor contamination and presence of a graft-versus-tumor effect. For this reason, patients who relapse after ASCT are often considered candidates for allogeneic bone marrow transplantation. However, there is limited knowledge on the outcome of alloBMT in patients who relapse after ASCT. We retrospectively analyzed the outcome of 20 patients with malignant lymphoma (n = 14) and AML (n = 6) who underwent alloBMT after failing an ASCT. The median age was 30 (17-41) years and the interval from ASCT to alloBMT was 10.5 (2-25) months. Seventeen patients died between 0.3 to 11 months (median 2.0) after alloBMT, all due to BMT-related toxicities. Three patients remain alive and free of disease at 1.1, 1.2 and 2.5 years after alloBMT. Sixteen of the 18 evaluable patients (89%) developed grade II-IV acute GVHD. Patients undergoing alloBMT after ASCT have a very high treatment-related mortality and incidence of grade II-IV acute GVHD. Alternative treatments with salvage chemotherapy, radiation or investigational approaches should be considered in patients who relapse after ASCT.