Expression of the hyaluronan receptor LYVE‐1 is one of few available criteria used to discriminate lymphatic vessels from blood vessels. Until now, endothelial LYVE‐1 expression was reported to be restricted to lymphatic vessels and to lymph node, liver, and spleen sinuses. Here, we provide the first evidence that LYVE‐1 is expressed on blood vessels of the yolk sac during mouse embryogenesis. LYVE‐1 is ubiquitously expressed in the yolk sac capillary plexus at E9.5, then becomes progressively down‐regulated on arterial endothelium during vascular remodelling. LYVE‐1 is also expressed on intra‐embryonic arterial and venous endothelium at early embryonic stages and on endothelial cells of the lung and endocardium throughout embryogenesis. These findings have important implications for the use of LYVE‐1 as a specific marker of the lymphatic vasculature during embryogenesis and neo‐lymphangiogenesis. Our data are also the first demonstration, to our knowledge, that the mouse yolk sac is devoid of lymphatic vessels. Developmental Dynamics 237:1901–1909, 2008. © 2008 Wiley‐Liss, Inc.