A new approach is proposed for synthesizing the standard 12-lead ECG from three differential leads formed by pairs of proximal electrodes on the body surface. The method is supported by a statistical analysis that gives the best personalized positions of electrodes. The measurements from multichannel ECGs were used to calculate the differential leads. Our algorithm searches for optimal differential leads and the corresponding personalized transformation matrix that is used to synthesize the standard 12-lead ECG. The algorithm has been evaluated on 99 multichannel ECGs measured on 30 healthy subjects and 35 patients scheduled for elective cardiac surgery. It is shown that the algorithm significantly outperforms the synthesis based on the EASI lead system with medians of correlation coefficients greater than 0.954 for all 12 standard leads. To determine the optimal number of differential leads, the syntheses for two, three, and four differential leads were calculated. The analysis shows that 3 is the optimal number of differential leads for practical applications. Because of the proximity of the differential electrodes, the proposed approach offers an opportunity for the synthesis of a standard 12-lead ECG with wireless electrodes.