The RhoGTPase Rac1 is activated in a polarized fashion and controls cell motility. We previously showed that Rac1 binds the PP2A inhibitor SET and recruits nuclear SET to the cytosol. We show that a SET mutant, lacking a nuclear localization signal, SET(ΔNLS), promotes cell spreading and motility. This was accompanied by an increase in the number and frequency of membrane ruffles. Pharmacological inhibition of PP2A did not mimic the effects of SET(ΔNLS), however, we found that expression of SET and SET(ΔNLS) increases the levels of the MAP kinases ERK1 and ERK2.