The lymphatic vasculature forms a second circulatory system that drains extracellular fluid from the tissues and provides an exclusive environment in which immune cells can encounter and respond to foreign antigen. Although equally important for the functioning of both the cardiovascular and immune systems, there is only a rudimentary knowledge of the molecular biology of lymphatics, owing to longstanding difficulties in identifying and isolating lymphatic endothelial cells. Recently, however, a number of interesting molecules have been identified that may be exploited as markers for lymphatic endothelium, including the hyaluronan receptor LYVE-1, the subject of this review. This article considers the biology of LYVE-1 and outlines how recent research into this molecule is providing new insights into the nature of lymphatics and their role in tumor metastasis.