The objective of this research is to derive the lightest-weight solution from the original vehicle model by finding the optimized spot-weld layout and body panel thickness, while keeping the body stiffness and number of spot welds constant. As the first step, a method of deriving the optimal layout of spot welds for maximizing body stiffness was developed by applying the topology optimization method. As a result, the effect of the spot-weld layout on body stiffness was clarified. In the case of the body used for this research, body stiffness was improved by about 10% with respect to torsion and vertical and lateral bending. The lightest-weight specification was then derived by simultaneously optimizing both the spot-weld layout and body panel thickness, while maintaining the same body stiffness as that of the original vehicle. As the final result, the body weight was reduced by about 20% by utilizing the improvement of body stiffness in the first step to reduce the body panel thickness.