Heparan sulfate proteoglycans (HSPGs) are important regulators of cell adhesion and cell signaling. The specific functions of these molecules are determined by both the core protein and the structure of the attached heparan sulfate chains. There is mounting evidence that HSPGs are remodeled by enzymes present on the surface of tumor cells or within the extracellular compartment. This remodeling within the tumor microenvironment leads to structural and functional alterations in HSPGs that regulate the behavior of tumor cells, including their growth and metastatic properties. This mini-review focuses on the effects of sheddases, endosulfatases and heparanase on syndecan-1 function and how this controls the behavior of myeloma tumors. ©2005 FCCA (Forum: Carbohydrates Coming of Age).