Breast cancer frequently metastasizes to bone via a process that is apparently facilitated by increased bone turnover.(6,38) In a previous study we demonstrated that primary breast tumor xenografts formed in the mammary fat pads of SCID mice expressing high levels of heparanase stimulated bone resorption with no evidence of any detectable tumor cells within the bone.(12) This study was performed to determine the mechanism for the distal osteolysis mediated by the heparanase-expressing tumor cells. Here, HPSE is linked to breast cancer.