Chondroitin sulfate proteoglycans (CSPGs) such as versican accumulate in tumor stroma and play a key role in tumor growth and invasion. The high expression of CSPGs in fast growing tissues and cells is correlated with chondroitin sulfate (CS) chains and the sulfation pattern. The negatively charged CS chains interact with a large number of ligands and receptors and activate signalling pathways which stimulate tumor growth. However, the role of chondroitin sulfate in cancer promotion seems to be controversial, as recent studies support the use of modified CS as a potent anticancer agent. In this review, the biological roles of CSPGs in cancer and the anticancer effects of modified CS are presented and discussed.