Tumor-reactive lymphadenopathy in sentinel lymph nodes has been observed for decades, but alterations of the lymphatic channels and vasculature in these nodes prior to the arrival of metastatic tumor cells remain unexplored. By inoculation of tumor cells into the left hind foot-pads of nude mice or immunocompetent mice, the authors show that tumor-reactive lymphadenopathy can be induced in the popliteal lymph node of the tumor-bearing limb, which is the sentinel lymph node in this model. The authors find that, during tumor-reactive lymphadenopathy, dilation of lymph sinuses as well as morphological and functional alterations of high endothelial venules within the sentinel lymph node can be induced by the primary tumor prior to the arrival of metastatic cancer cells. Moreover, the proliferation rate of the endothelial cells in the high endothelial venules is also increased before metastasis. For details, see the article by Qian et al. on page 10365 of this issue.