The hyaluronan-mediated motility receptor, also known as RHAMM, was initially identified as a soluble protein that could be released by sub-confluent migrating cells, promoting cell motility and invasion via interactions with hyaluronan (HA) and the cell surface. While RHAMM is normally poorly expressed in most normal tissues and is not required for embryonic development or normal cell homeostasis functions, its expression is increased during wound repair in response to hypoxia and fibrogenic factors. However, its overexpression is transforming in multiple types of cancers and is required for maintaining RAS transformation. RHAMM associates with BRCA1 and BARD1, attenuating the mitotic-spindle-promoting activity of RHAMM, which may contribute to tumor progression by promoting genomic instability.