The acquisition of invasive behaviour enables the tumour cells to move into either the surrounding tissue or the vasculature and thereby spread to other parts of the body. The focus of our research is investigating why cancer cells become invasive and how they move. To study cell motility in this environment we perform intravital multi-photon confocal imaging of tumours in anaesthetised mice. This enables the heterogeneous behaviour of cancer cells to be studied as they transit between primary and secondary sites. We have used a range of transcriptional reporters to evaluate the signalling and differentiation status of invasive and metastatic melanoma cells. This work demonstrates that differentiation hierarchies remain even in aggressive melanoma models. By using transgenic hosts we can also visualise the interplay between tumour cells, leukocytes, stromal fibroblasts and endothelial cells. We will present new data about endothelial cell organisation and dynamics in different melanoma micro-environments and the relationship to invasive cancer cell behaviour.