Metastasis is the major cause of death from cancer and metastasis to the lung in breast cancer is difficult to treat and heterogeneous in nature, complicating its management (1-5). We recently utilized whole transcriptome technologies to define the full complement of differentially expressed kinases and phosphatases in HER2+ breast cancer: in the primary tumor, and in metastasis to the CNS (6-8). Here we utilize whole transcriptome technologies (9, 10) to measure total transcription in the lung metastases of humans with breast cancer, integrating this with transcriptome data from a cell culture model of lung metastatic potential. We identify here a therapeutic target based on its differential expression and up-regulation upon metastasis to the lung in humans with breast cancer, SHB, as a candidate therapeutic target for the medical management of lung metastasis.