A 47-year-old woman with no history of CAD presented with an episode of left-sided atypical chest pain. Her work-up was negative for acute MI. She underwent a myocardial perfusion Tc-99m tetrofosmin SPECT study to rule out myocardial ischemia. The SPECT images revealed a small nonreversible mid-anteroseptal perfusion defect. For additional evaluation coronary computed tomography angiography was performed. This revealed normal coronary arteries and demonstrated a small muscular ventricular septal defect which corresponded to the location of the fixed perfusion defect on the SPECT images. The presence of the ventricular septal defect should be considered in differential diagnosis of an isolated fixed septal perfusion abnormality on SPECT images in patients with no history of prior MI.