Myocardial perfusion scintigraphy is a well validated noninvasive method of evaluating for significant coronary artery disease, especially in cases where electrocardiographic changes are nondiagnostic, including left bundle-branch block. However, such testing with a technetium Tc 99m agent is often confounded by left ventricular septal-based false-positive perfusion defects. These defects can be either reversible or irreversible in the septal or anteroseptal wall, problematically then, in the territory supplied by the left anterior descending coronary artery. Mechanisms explaining false-positive defects include decreased perfusion via impaired microvessel flow and normal perfusion with apparent decrease in counts in a relatively thin septum (partial-volume effect). Key findings in myocardial perfusion images in the presence of left bundle-branch block that define true positives (ischemia) are reversible perfusion defects (especially at end diastole), a concomitant apical defect, and systolic dysfunction matching the perfusion defect.