In analogy with immune cells, breast cancer dissemination into the lungs is presumed to require chemokine receptors, although their expression on the surface of tumors is rarely shown and remains poorly defined. Olkhanud and colleagues, using novel formulations that specifically deplete chemokine receptor–expressing cells, demonstrate that lung metastasis is a feature of only a proportion of the tumor cells that express CCR4. Depletion of CCR4-expressing cells completely abrogated both the chemotactic responses to CCL17 and CCL22 and metastasis into lungs without affecting the growth of a primary tumor in the mammary glands. Nevertheless, although this inherent capacity to chemotax was necessary, it alone was not sufficient to produce metastasis in the absence of an active participation of CCR4-expressing regulatory T cells (Tregs). In fact, the primary tumor growing in the mammary gland prepared its metastasis target site by inducing CCL17 and CCL22 production in the lungs. As a result, CCR4⁺ tumor cells metastasized into the lungs together with CCR4⁺ Tregs. The latter was essential for the protection of metastasizing cells from NK cells by directly killing them utilizing galectin-1. The cover image is an immunohistochemistry staining for expression of CCL17 in human lungs with metastatic breast cancer. For details, see the article by Olkhanud and colleagues on page 5996 of this issue.