Breast cancer inflicts casualties by metastasizing to a variety of distant organs, including lung, bone, liver and brain. Although the tissue tropism for breast cancer metastasis has been recognized and studied for along time, the molecular and cellular mechanisms underlying this process remain sketchy. Recent technological breakthroughs in functional genomics, in vivo imaging, and genetic manipulation of cancer cells in animal metastasis models have enabled the discovery and analysis of tissue-specific metastasis genes. These genes play vital roles in mediating tumor-stroma interactions during metastasis and are likely candidates for therapeutic interventions. Analysis of tissue-specific metastasis not only enriched our understanding about the malignancy of breast cancer, but also provided elegant experimental support for the century-old "seed and soil" hypothesis.