The RhoGTPases constitute a large family of small GTP binding proteins that police many sensitive crossroads in diverse cellular functions. Therefore, it would not be surprising if aberrant RhoGTPase function led to perturbed growth and differentiation, including carcinogenesis and cancer progression. The evidence for a causative connection between RhoGTPases and primary human cancers is still weak but there are increasing findings to support this link. An appreciation of this connection is timely and important to alert readers to the possibilities of new disease mechanisms and new ways to diagnose and treat cancer.