Versican, a large extracellular matrix proteoglycan accumulates in tumor stroma and plays a key role in both malignant transformation and tumor progression. Increased versican expression has been observed in a wide range of malignant tumors, and has been associated with both cancer relapse and poor patient outcomes in breast, prostate, and many other cancer types. Through negatively-charged chondroitin and dermatan sulfate side chains or interactions of the G1 and G3 domains, versican is able to regulate many cellular processes including cell adhesion, proliferation, apoptosis, migration, angiogenesis, invasion and metastasis. In this review, the biological roles that versican plays in cancer development are presented. Therapeutic targeting of versican in malignant tumors is also discussed.