Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that the apolipoprotein B mRNA editing enzyme catalytic subunit 3A, APOBEC3A, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that APOBEC3A was also differentially expressed in brain metastatic tissues. APOBEC3A mRNA was present at increased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of APOBEC3A in primary tumors of the breast was correlated with patient overall survival, more significantly in lymph node negative patients than in lymph node positive patients. Modulation of APOBEC3A expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer. APOBEC3A differential expression in lymph node metastatic tissues raises the question of why a human papillomavirus restriction factor (6, 7) is up-regulated during metastatic progression in human breast cancer.