Mass minimization is a key objective for the design of racing motorcycle wheels. The structural optimization of a front motorcycle wheel is presented in the paper. Topology Optimization has been employed for deriving optimized structural layouts. The minimum compliance problem has been solved, symmetry and periodicity constraints have been introduced. The wheel has been optimized by considering several loading conditions. Actual loads have been measured during track tests by means of a special measuring wheel. The forces applied by the tire to the rim have been introduced in an original way. Different solutions characterized by different numbers of spokes have been analyzed and compared. The actual racing wheel has been further optimized accounting for technological constraints and the mass has been reduced down to 2.9 kilograms.