Numerous pathologic events are required for a tumor cell to metastasize to bone and develop either a lytic or blastic lesion. These events initiate in the local environment where alterations in the expression of adhesion molecules such as the integrins, CD-44, and other factors permit cells to migrate and exodus the local environment. Adhesion molecules help organize the actin cytoskeleton and the formation of podosomes, which are cytoplasmic protrusions involved in cellular migration. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, and other proteases degrade Type iV collagen in the vascular basement membrane and permit egress into the vascular and lymphatic systems.