The usefulness of the right precordial unipolar leads and the value of the bipolar lead CM5 in the detection of coronary artery disease (CAD) with exercise electrocardiographic (ECG) test are not well documented. The objective of this study was to evaluate the diagnostic performance of leads V4R and CM5. The study population comprised 579 patients referred for a bicycle exercise ECG test in the Finnish Cardiovascular Study. Patients were divided into three groups: angiographically proven CAD (CAD, n = 255), no CAD by angiography (NoCAD, n = 126), and low likelihood of CAD (LLC, n = 198). The maximum ST-segment depression at peak exercise was used as a parameter, and the diagnostic accuracy of different leads was assessed by receiver operating characteristic (ROC) analysis. Sensitivity and specificity values at a cut-off criterion of -0.10 mV ST-segment, 1-mm ST depression, were determined. According to the results, incorporating lead V4R with the standard leads decreased the ROC area from 0.71 to 0.69 (comparison CAD versus LLC) and from 0.55 to 0.53 (comparison CAD versus NoCAD) and had no effect on sensitivity or specificity. Adding lead CM5 to the standard leads did not affect the ROC area but increased the sensitivity and decreased the specificity. In conclusion, the use of right precordial lead V4R along with the standard 12-lead system does not improve the performance of the exercise ECG in diagnosing CAD. Adding lead CM5 to the standard leads increases the sensitivity but does not change the overall diagnostic performance.