Variance electrocardiogram (ECG) is a newly developed method by which resting ECG is registered with 24 leads during 220 beats. The temporal beat-to-beat QRS microamplitude variability is computed and a nondimensional diagnostic variance ECG coronary artery disease (CAD) index is derived from it. Consecutive outpatients (n = 160) were referred to myocardial scintigraphy (SPECT) investigation for the evaluation of angina pectoris. The variance ECG CAD index was compared with a symptom-limited exercise stress test and SPECT during and after the exercise test and with coronary angiography (n = 67). Discriminant accuracy was tested with receiver-operating characteristics (ROC). Relative to angiographic coronary pathology (prevalence 0.85), diagnostic information for the variance ECG CAD index and for SPECT were both p < 0.001, while the outcome of the exercise stress test was non-contributory. Prevalence of persistent or transient perfusion defects at SPECT was 0.59. The exercise stress test had a diagnostic capacity of p < 0.01 for transient perfusion defects and variance ECG CAD index showed a high diagnostic performance (p < 0.001) for persistent perfusion defects. Overall pathology at SPECT was better (p < 0.05) identified by variance ECG CAD index than by symptom-limited exercise stress test. It was concluded that in this high prevalence population the variance ECG CAD index has a diagnostic capacity at least as good as that of SPECT and better than that of the exercise stress test. The variance ECG CAD index was strongly diagnostic for persistent perfusion defects while exercise stress test was slightly diagnostic for transient perfusion defects. Therefore, the two tests provide complementary diagnostic information.