Cell polarization can occur in the absence of any spatial cues. To investigate the mechanism of spontaneous cell polarization, we used an assay in yeast where expression of an activated form of Cdc42, a Rho-type guanosine triphosphatase (GTPase) required for cell polarization, could generate cell polarity without any recourse to a preestablished physical cue. The polar distribution of Cdc42 in this assay required targeted secretion directed by the actin cytoskeleton. A mathematical simulation showed that a stable polarity axis could be generated through a positive feedback loop in which a stochastic increase in the local concentration of activated Cdc42 on the plasma membrane enhanced the probability of actin polymerization and increased the probability of further Cdc42 accumulation to that site.