In women, obesity is linked to 20% of all cancer deaths. The molecular mechanisms are largely unknown but the risk of invasive/metastatic disease with obesity may include elevated levels of hormones like leptin, IGFs and estrogens. Leptin is a pleiotropic hormone primarily synthesized by adipose tissues and circulating levels are higher in obese people (200ng/ml) than non obese people (10ng/ml-30ng/ml). We examined the effect and mechanism of leptin treatment on the metastatic and cancer stem cell (CSC) characteristics of human breast cancer cells in vitro. Leptin receptor (LEPR) was found to be highly expressed in more invasive breast cancer cells (29-fold higher mRNA expression in MDA-MB-231 than MCF7, P<0.0001). To assess the effect of leptin treatment on metastatic capacity of breast cancer cells, MCF7 cells were treated for 14 days with leptin. Compared to untreated MCF7 cells, treatment with 200ng/ml of leptin increased breast cancer cell motility (scratch assay, 1.85-fold, P=0.0018) and invasiveness (2.45-fold, P=0.0021). Leptin treatment induced epithelial to mesenchymal transition (EMT), decreasing CDH1 mRNA (0.1-fold, P=0.002) and increasing SNAI2 mRNA (4.1-fold, P<0.0001) compared to the untreated cells. Leptin also induced aldehyde dehydrogenase activity by 6.4 fold (ALDEFLUOR, P=0.0069) and increased colony forming capacity (mammosphere assay, 2.03-fold, P<0.0001) indicating an increased stem-like phenotype. Co-treatment of leptin and neutralizing antibody against TGFB1 abrogated these effects, indicating that the induction of EMT and CSC characteristics was mediated via TGFB1. This study indicates the significance of leptin in contributing to the poor outcomes of breast cancer in obese patients.