ECG changes during exercise stress testing, such as false-positive ST-segment depression and disappearance of the delta wave, are reported in patients with the Wolff-Parkinson-White (WPW) pattern. We present a case of exercise testing in a 53-year-old man with WPW syndrome with ischemic-appearing ECG changes and normal nuclear stress perfusion study findings who was thought to be at clinically low risk for having significant coronary disease. A literature review is discussed. Although ST-segment depression typical for ischemia occurs in half of the patients in whom WPW syndrome is reported, exercise testing is still an important tool in their evaluation. Data other than ECG response can be interpreted in the context of clinical history and physical examination findings to stratify the risk of coronary disease. Complete and sudden disappearance of the delta wave has been seen during exercise in 20% of patients with WPW syndrome and can identify those who are at low risk for sudden arrhythmic death.