Receptor tyrosine kinase-like orphan receptor (ROR), consisting of ROR1 and ROR2, is a conserved family of receptor tyrosine kinase superfamily that plays crucial roles during embryonic development with limited expression in adult normal tissues. However, it is overexpressed in a range of hematological malignancies and solid tumors and functions in cellular processes including cell survival, polarity, and migration, serving as a potential target in cancer immunotherapy. This review summarizes the expression and structure of ROR in developmental morphogenesis and its function in cancers associated with Wnt5a signaling and highlights the cancer immunotherapy strategies targeting ROR.