['To study the clinical impact of a very high coronary artery calcium score (CAC >1000) in patients with no known coronary artery disease (CAD) and normal single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). The secondary aim was to evaluate whether triple vessel disease would support the notion of balanced ischaemia as an underlying mechanism of false negative SPECT MPI in patients with very high CAC.', 'No data exist on the clinical value of high CAC in patients with normal SPECT MPI.', '50 patients with suspected CAD and normal stress/rest SPECT MPI and CAC >1000 prospectively underwent invasive coronary angiography as the standard of reference. Coronary lesions with ≥50% luminal diameter narrowing on invasive coronary angiography were considered to represent significant stenosis.', 'The median total CAC was 1975 (range 1018-8046). In 37/50 (74%) patients, coronary angiography revealed one-vessel disease (1-VD) (n=15), 2-VD (n=10) or 3-VD (n=12). Twenty-six revascularisations (percutaneous coronary intervention/coronary artery bypass grafting) were performed in seven (6/1), seven (6/1) and 12 (7/5) patients with 1-VD, 2-VD and 3-VD, respectively.'] Does very high coronary calcium score unmask obstructive coronary artery disease in patients with normal SPECT MPI?