Microenvironmental stimuli can influence the malignant phenotype of cancer cells. Notably, the altered biosynthesis of hyaluronan, a constituent of the extracellular microenvironment, has been implicated in the progress and metastasis of carcinomas. The discovery of hyaluronan synthase (HAS) genes, which encode the key enzymes in hyaluronan biosynthesis, has enabled great strides in understanding the mechanism underlying altered hyaluronan production in cancer and the involvement of this polysaccharide in tumor progression. Recent studies using HAS transgenic mice have provided evidence that overproduction of hyaluronan in mammary tumors accelerates tumor growth through the recruitment of stromal cells and vasculature, revealing further insight into how increased hyaluronan influences the malignant behaviors of cancer cells.