© 2018 Italian Federation of Cardiology. Aims Prior studies using stress myocardial perfusion imaging (MPI), which examined the association between obstructive epicardial coronary disease and presence of myocardial ischemia did not provide a detailed assessment on a regional level. We examined this relationship in a large population of patients in whom the coronary anatomy was defined by invasive coronary angiography. Methods We retrospectively extracted details on individuals undergoing MPI with single photon emission computed tomography (SPECT) who had coronary angiography within 12 months. A 17-segment model for native coronary anatomy and a 7-region model for myocardial perfusion were used with a dedicated matching algorithm. Results A total of 2564 patients were included, yielding a total of 6279 stenoses matched with 17 948 myocardial regions. From such a cohort, 151 (5.9%) patients had normal perfusion, 1878 (73.2%) had myocardial ischemia (reversible defects), 260 (10.1%) had myocardial necrosis (scar or fixed defects), and 275 (10.7%) had ischemia and necrosis. At per-patient analysis, significant angiographic disease was more common in the ischemic group (prevalence between 69.6 and 80.0%) than other groups. At per-region analysis, abnormal perfusion in the coronary-specific regions varied depending on location of stenosis; it was 96% for left main disease, 81% for proximal left anterior descending disease, 85% for proximal left circumflex disease, and 82% for proximal right coronary artery disease and 60% for posterior descending artery disease. Conclusion The correlation between significant coronary stenosis and presence of corresponding regional perfusion abnormality depends on the location of the lesion and the corresponding myocardial region.