Hematopoietic cells, and more particularly, dendritic cells are so called "professional" antigen-presenting cells, which prime CD8(+) T-cell responses. They achieve this by taking up antigens and presenting them to CD8(+) T cells in the draining lymph nodes. This process is called cross-presentation (XP). For most developing tumors, XP of tumor antigens results in CD8(+) T-cell tolerance. In addition to XP, direct presentation by any kind of cell can also occur in lymph nodes. We discuss here how a non-hematopoietic cell can efficiently prime CD8(+) T cells by direct presentation in lymph nodes. Such a T-cell activation pathway is likely to be of importance for the control of cancer metastases that use the lymphatic system to spread.