Takotsubo cardiomyopathy (TTC) is still an under-recognized disease and little data exists on the coexistence of TTC and obstructive coronary artery disease. Our patient case of an 80-year-old female lady highlights the impact of a positron emission tomography/computed tomography (PET/CT) follow-up imaging study to delineate this unique entity from acute coronary syndrome (ACS). Furthermore, we show for the first time that coronary flow reserve and myocardial blood flow is globally impaired in TTC and not only restricted to the non-contracting parts. This indicates a global microcirculatory impairment effect of the heart in the acute stage of TTC. Our case also demonstrates that a transient metabolic defect is also involved in this disease. Follow-up imaging by PET/CT in our patient case unmasked TTC and facilitated to exclude the differential diagnosis of ACS.