Abstract Mason-Likar or proprietary reduced lead (RL) configurations are used for continuous 12-lead electrocardiogram (ECG) monitoring. Because each RL set has a different electrode configuration and derivation, they are inherently different and should not be compared with each other or with the Mason-Likar or standard ECG to determine changes in an individual over time. Recently, cases have been reported regarding misdiagnosis resulting from such invalid comparisons. This article addresses several relevant questions and presents data collected from 559 subjects (one third, prior myocardial infarction; one third, left ventricular hypertrophy; one third, healthy controls) comparing standard limb leads with body surface potential map (BSPM) leads. We conclude the following: (1) There are few circumstances that justify the use of RL 12-lead ECGs; the convenience should be weighed by the risk of misdiagnosis resulting from serial comparison of nonequivalent ECGs. (2) When RL monitoring is justified, standardization of one universally adopted method would reduce confusion about multiple proprietary lead configurations and minimize invalid ECG comparisons in individuals treated in multiple hospital units with different manufacturers' cardiac monitors. (3) Standard limb lead P-QRS-T waveforms correlate highly with BSPM leads located outside standard unipolar precordial lead sites. Until it is clear that “optimum” BSPM lead sites do not overlap with ECG information already contributed from standard limb leads, it is premature to recommend alternative lead sites for ECG monitoring.