Treatment strategy in patients with suspected coronary artery disease (CAD) is driven by symptomatology in combination with diagnostic evaluation of the extent and/or severity of atherosclerosis in the coronary arteries and ischemia in the myocardium, i.e., the anatomic and functional correlates of CAD. Whereas multislice row computed tomography (MSCT) has the advantage of detecting coronary atherosclerosis at its earliest stages, thereby allowing initiation of appropriate therapeutic measures well before development of obstructive CAD, myocardial perfusion imaging (MPI) SPECT can clarify the hemodynamic consequences of the anatomic findings on MSCT based on a functional assessment of myocardial blood flow. There is a lack of correlation between coronary artery calcium (CAC), coronary artery stenosis, and MPI SPECT. Therefore CAC scoring and stress MPI should be thus considered complementary approaches rather than exclusionary in the evaluation of the patient at risk for CAD. The integration of anatomic and functional information may provide additional information for the clinician by the improved risk stratification and diagnostic accuracy of integrated techniques. The majority of previous studies are based on a sequential flowchart, starting with either SPECT or CAC scoring that finally directs the therapeutic strategy. Patients at low risk for CAD can be selected for primary prevention, and patients at high risk for CAD can be directly selected for coronary angiography (CAG). The remaining group of patients at intermediate risk for CAD can be substratified into lower- and higher-risk categories based on the presence or absence of stress-induced ischemia on MPI SPECT and CAC scoring. An integration of SPECT and CAC as a starting point for CAD detection in symptomatic patients at intermediate risk for CAD may facilitate a tailored diagnostic as well as therapeutic approach. Finally, using SPECT/CT, MPI SPECT, and CAC findings may be completed with CT angiography. The development of SPECT/CT hybrid systems is therefore of important value for the nuclear cardiology armamentarium. This editorial commentary outlines a diagnostic pathway of integrated SPECT/CT for CAD assessment in symptomatic patients at intermediate risk for CAD.