Abstract It may not always be possible to record all precordial leads of the standard 12-lead electrocardiogram (ECG). Especially in monitoring situations, a minimal lead set from which the 12-lead ECG can be reconstructed, would be valuable. This article assesses how well missing precordial leads could be synthesized from the remaining leads of the 12-lead ECG. A total of 2,372 diagnostic 12-lead ECG recordings were obtained from subjects with chest pain suggestive for acute myocardial infarction. Representative average beats were computed from the digital 12-lead ECG recordings with our Modular ECG Analysis System. The recordings were divided into a learning set and a test set. We considered all lead sets with one or more precordial leads removed, but always including limb leads I and II. By using the learning set, general reconstruction coefficients were computed to synthesize the missing precordial leads to each lead set. Performance of the synthesis was assessed by cross correlation between the original and the reconstructed leads. Also, patient-specific reconstruction coefficients were derived for each ECG in the test set and correlations were determined. High correlation coefficients were found with both reconstruction techniques. For different sizes of lead sets, the best patient-specific reconstructions had higher correlation values than the general reconstructions. For example, when 2 precordial leads were excluded, the best patient-specific median correlation was 0.994 compared to 0.963 for the best general reconstruction correlation. General reconstruction allows synthesis of 2 or 3 excluded precordial leads in good approximation. When patient-specific reconstruction can be applied, a minimal lead set including the limb leads and only 2 precordial leads suffices.