Zebrafish models of cancer have emerged as powerful tools to image cancer progression and metastasis. When coupled with the robust genetic tools available in the model, it is an ideal system to dissect the in vivo interactions between tumor cells and their surrounding microenvironment. In a screen for stromal factors supporting melanoma outgrowth, we have identified signals from the surrounding adipocytes as being major drivers of melanoma progression. The seminar will discuss the nature of the melanoma-adipocyte interactions including novel ways of interrupting this cross-talk.