The breast continues to be reported as a site of resistant leukemia despite current curative protocols. To characterize disease behavior and potential for lengthy survival after breast relapse, a study was undertaken of 153 cases reported between 1969 and 2005. Authors were contacted for follow-up. There were 105 AML and 48 ALL cases identified. Ninety percent of female patients were younger than 50 and leukemia was temporally related to pregnancy in 13. Eight cases were males. Remissions were typically of short duration, principally due to further extramedullary relapses, in 3 main sites in both AML and ALL: contralateral breast, gynecologic organs, and CNS. However, there are cases of disease-free survival up to 26+ years after intensive treatment. Leukemia growing in the breast may follow a distinctive pattern, and prompt initiation of intensive multi-cycle treatment, assuming occult site involvement, with consideration of CSF prophylaxis, should increase the potential for disease eradication.