The use of multiphoton imaging in living undissected mammary tumors reveals that macrophages initiate invasion and intravasation using paracrine signaling pathways that have been correlated with metastatic outcome. These results indicate that perivascular macrophages determine the metastatic potential of tumor cells and are an important drug target for cancer therapy. Figures counterclockwise from the top show: a 300-μm-thick reconstruction of a mammary tumor of the mouse showing blood vessels in red and macropages in green; green perivascular macrophages surrounding a blood vessel; and a high magnification image of a single perivascular macrophage with engulfed red dextran particles. For details, see the article by Wyckoff et al. on page 2649 of this issue.