During hepatic metastasis, tumor cells are exposed to the sinusoidal environment, involving endothelial cells, Kupffer cells, pit cells (NK cells) and fat-storing cells [1]. It is known that Kupffer cells and pit cells play a direct role in killing metastasizing colon carcinoma cells [1,2]. Only few studies describe the interactions of Kupffer cells and tumor cells within the first 24 hrs of metastasis [3-6]. The importance of this early phase lies in the substantial but not complete killing of tumor cells. Also, at later stages, when different elements of host defense are involved, it is apparent that the local immune system is not capable of preventing metastasis. Investigating rare cellular events is facilitated by studying the full depth of thick sections with confocal laser scanning microscopy. Complicated preparation and histochemical procedures and a low sampling-volume [7] characterize classical microscopic methods. In contrast, confocal laser scanning microscopy (CLSM) has the ability to study thick sections (100 micrometers), gathering 3D information and allowing the use of different fluorescent probes for different variables [8]. Localization of cells can be done by immunohistochemistry, by labeling cells in vitro prior to injection or by labeling them in vivo. The anti-metastatic function of Kupffer cells was studied by labeling tumor cells with the lipophilic probe DiO in vitro and Kupffer cells with fluorescent latex particles in vivo.