Human Ly-6/uPAR molecules are a superfamily composed oftwo subfamilies; one is the membrane bound proteins with aGPI-anchor and the other are secreted proteins without theGPI-anchor. Ly-6/uPAR molecules have remarkable amino acidhomology through a distinctive 8-10 cysteine-rich domain thatis associated predominantly with O-linked glycans. Thesemolecules are encoded by multiple tightly linked genes locatedon Chr. 8q23, and have a conserved genomic organization.Ly-6/uPAR molecules have an interesting expression patternduring hematopoiesis and on specific tumors indicating thatLy-6/uPAR molecules are associated with development of theimmune system and carcinogenesis. Thus, Ly-6/uPAR moleculesare useful antigens for diagnostic and therapeutic targets.This review summarizes our understanding of human Ly-6/uPAR molecules with regard to molecular structure as well aswhat is known about their function in normal and malignanttissues and suggest Ly-6/uPAR molecules as target antigens forcancer immunotherapy.