Breast carcinoma is the most frequent cancer in women, affecting one million yearly. In the past decades there have been great improvements in surgery, screening and therapy that have led to dramatic changes in the 5-year overall survival rates for breast cancer patients. Unfortunately, while primary tumors can be efficiently removed by surgical intervention, there are essentially no successful therapeutic options for metastatic disease. Currently, the most relevant clinical and experimental questions in the breast cancer field revolve around metastasis. Can we identify specific molecules and pathways contributing to metastatic spread and to tumor cell survival and growth in distant sites? Once identified, can we design appropriate metastatic therapies? My presentation will focus on these questions. I will discuss our studies aimed at uncovering new molecular mechanisms involved in the crosstalk between tumor cells and the bone marrow (BM) environment. For this, we performed analyses comparing transcriptomes of tumor cells growing in the mammary fat pad, versus tumor cells isolated from the bone environment, as well as analyses comparing transcriptomes of different cell populations from the BM environment from tumor-bearing and tumor-free mice. I will also discuss Memo, a protein that our our group originally identified as being essential for breast cancer cell motility in response to activation of several receptor tyrosine kinases. We have recently discovered that Memo is a metal-binding enzyme that requires Cu(II) for its oxidase-like activity. Memo KD in different breast cancer models impairs in vivo spontaneous lung metastasis from xenografts. Moreover, IHC carried out on a breast cancer TMA consisting of >400 tumor samples revealed significantly high Memo expression in > 40% of tumors; elevated Memo levels are prognostic of poor outcome.