Dedicated cadmium-zinc-telluride cardiac cameras have been shown to provide accurate measurements of absolute myocardial blood flow and flow reserve when PET is not available. We report the case of a 66-year-old woman who underwent 1-day stress/rest myocardial perfusion imaging (MPI) for coronary artery disease (CAD) screening. Relative MPI analysis was normal, whereas low-dose CT showed high calcium score. Myocardial blood flow and flow reserve were strongly impaired in all territories. Coronary angiography confirmed extended CAD. Flow parameters derived from cadmium-zinc-telluride SPECT MPI acquisition and calcium scoring can improve diagnostic accuracy and confidence of CAD.