Mental stress–induced myocardial ischemia (MSIMI) has been described in patients with acute coronary syndrome (ACS). We reported the case of a patient admitted with ACS and MSIMI related to generalized anxiety disorder (GAD). Myocardial perfusion imaging (MPI) after exercise stress and computed tomography coronary angiography showed normal results. In contrast, MPI with mental stress documented MSIMI. He began to improve 7 days after starting escitalopram and remained without angina at 1-year follow-up. These data suggest the applicability of mental stress radionuclide imaging for the detection of MSIMI in patients with ACS and GAD, even in normal coronary arteries.