The mode of invasion of liver tissue by mammary carcinoma cells was studied after the injection of such cells into the portal system of intact, isologous mice. The initial invasion was investigated during the first hours after the injection, before most tumor cells were eliminated. Later stages of invasion were examined in the border areas of tumor nodules developing after 8–12 days. The tumor, maintained by subcutaneous transplantations, was characterized by acinus-like structures in which most cells were connected by junctions. A suspension, prepared mechanically, contained not only monodispersed cells, but also tiny, compact clumps of cells with junctions at the tumor-fluid interface. Immediately after the injections, large emboli with essentially the same structure as these tiny clumps formed in the hepatic portal branches. In the adjacent sinusoids, these emboli had thin extensions in which the tumor cells had no junctions. Only tumor cells in sinusoids invaded the liver parenchyma. Discontinuities in the endothelial cells probably developed first, and subsequently tumor-cell pseudopods were extended into the underlying hepatocytes. In the border areas of the tumor nodules developing later, tumor cells protruded deeply into surrounding hepatocytes. Junctions between hepatocytes and tumor cells were common, especially associated with intercellular lumina surrounded by both tumor cells and hepatocytes. With time, hepatocytes were excessively deformed by the tumor cells. However, no active destruction of hepatocytes by tumor cells was recorded.