Matrix metalloproteinases (MMPs), a family of zinc-binding endopeptidases, play important roles in cancer proliferation and dissemination, and may be further associated with other diseases. In particular, membrane-type MMPs (MT-MMPs) are crucial for cancer cell invasion. In this report, we summarize the current views on the role of MT-MMPs in cancer dissemination. The regulated and restricted degradation of the extracellular matrix (ECM) surrounding the tumor surface is a trigger event for cell protrusion and invasion. This is thought to be primarily organized by MT-MMPs, since a shift in balance between cell adhesion molecules, ECM and proteolysis at the focal cell surface may result in conditions especially suitable for cancer cells to progress and invade the ECM. To resolve the physiological mechanisms of cancer invasion and migration, molecular milieu surrounding the MT-MMPs expressed on tumor cell surfaces should be further examined for each cell type, which may consequently provide a novel clinical tool to regulate cancer behavior.