We have examined the effect of chronic, physiological leptin treatment on the metastatic and CSC-like characteristics of breast epithelial and cancer cells, and have discovered that promotion of invasiveness and CSC behavior by leptin is mediated through binding of TGFB1 to its receptor, increasing the likely contribution of leptin signalling to poorer outcomes in obesity, and adding to the list of pathways that may be readily targeted in obese cancer patients. The gene discussed is TGFB1; the disease is obesity due to melanocortin 4 receptor deficiency.