Wnt5a is one of the most extensively studied proteins of the Wnt family and is known to play an important role in cellular motility and proliferation. Wnt5a is a ligand of the receptor tyrosine kinase-like orphan receptor 1 (ROR1), an onco-embryonic protein expressed on chronic lymphocytic leukemia (CLL) B cells, and on a variety of solid tumors, but not on normal adult tissues. This mini-review summarizes recent results regarding the inhibition of effects of Wnt5a signaling by targeting ROR1.