Homeobox (HOX) genes play key roles in embryogenesis and tissue differentiation. Recently, a number of groups have reported altered HOX gene expression in breast cancer. However, the mechanism of HOX gene regulation and the search for direct targets of its transcriptional regulatory function have been minimally fruitful. Recently, Gilbert and colleagues reported that HOXA9 restrains breast cancer progression by upregulation of BRCA1, a tumor suppressor. This finding raises our hope that more, rather elusive targets of HOX genes important in tumor progression or suppression will be found in the future.