Of a group of 149 patients who underwent allogeneic stem cell transplantation using the "Mexican approach", a nonablative preparative regimen, 49 individuals developed bone marrow relapse, and 8 patients developed extramedullary relapse (EMR). All EMR cases presented in patients who received allografts for myeloid malignancies. In contrast, bone marrow relapses presented in patients with myeloid or lymphoid malignancies. EMR presented 60 to 1010 days after the allograft and appeared in 3 cases as subcutaneous nodules in different parts of the body, in the vertebrae in 3 cases, and in the kidney and the breast in 1 case each. One patient had both subcutaneous nodules and epididymis EMR. When EMR was noted, acute graft-versus-host disease (GVHD) had presented in 4 patients, and limited forms of chronic GVHD were present in 3 patients. All but 1 of the patients were full chimeras when the EMR ensued, and the EMR preceded an overt hematologic relapse in all but 1 of the patients. Patients who experienced an overt hematologic relapse died 20 to 180 days (median, 40 days) after the EMR. The only individual alive 240 days after relapse shows no evidence of a full-blown hematologic relapse. An EMR after allogeneic hematopoietic stem cell transplantation usually has a bad prognosis and presents mainly in individuals with high-risk malignancies.