RAB25, a member of the rat sarcoma (RAS) family of small GTPase, has been implicated in the pathophysiology of ovarian, breast and other cancers. Its role in endosomal transport and recycling of cell-surface receptors and signaling proteins presents a novel paradigm for the disruption of cellular pathways and promotion of tumor development and aggressiveness. Variations in structure and post-translational modifications control the localization of RAS superfamily proteins to specific subcellular compartments and recruitment of downstream effectors, allowing these small GTPases to function as sophisticated modulators of a complex and diverse range of cellular processes. Here, we review the link between RAB25 and tumor development and current knowledge regarding its possible roles in cancer.