Healthy cells are like skilled traffic controllers. They continually move proteins to and from the cellular destinations where they are needed, usually without mishap, through an elaborate system of endomembranes. Wheeler et al. show that a glitch in the traffic control system can help propel a cell toward malignancy (see the Perspective by Ferguson). RAB35, a protein previously implicated in endomembrane trafficking, is a key regulator of a well-known oncogenic signaling pathway. Mutations in RAB35 found in certain human tumors aberrantly activate this pathway and cause mislocalization of a factor that promotes cell growth.