The main purpose of the study was to evaluate the utility of technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography (Tc-99m sestamibi SPECT) in detection of cardiac involvement in systemic lupus erythematosus (SLE) or systemic sclerosis (SS) patients. Fifty SLE or SS female patients with cardiac symptom/sign such as chest discomfort and/or dyspnea and/or occasionally palpitation and 50 SLE or SS female patients without any cardiac symptom/sign were investigated using Tc-99m sestamibi SPECT during rest and stress after dipyridamole infusion. Twenty-five age- and sex-matched healthy females were also included as controls in this study. The results of Tc-99m sestamibi SPECT were classified into four types including normal, persistent perfusion defect (PD), reversible perfusion defect (RD), and reverse perfusion defect (RR). The results of Tc-99m sestamibi SPECT in the 25 healthy females were normal. Perfusion abnormalities were detected in 44/50 (88%) symptomatic SLE or SS patients. However, myocardial perfusion abnormalities were only detected in 19/50 (38%) asymptomatic SLE or SS patients (P value<0.05 by a chi2 test). However, for risk factor of coronary artery disease and abnormal resting EKG, the incidences were not significant between symptomatic and asymptomatic patients (P values >0.05 by a chi2 test). Tc-99m sestamibi SPECT is a useful noninvasive imaging modality to detect cardiac involvement in symptomatic or asymptomatic SLE or SS patients.