In patients with heart failure (HF) due to coronary disease, a combined evaluation of perfusion and glucose metabolism by cardiac single photon emission computed tomography (SPECT)/positron emission tomography (PET) can be used to distinguish viable from non-viable myocardium, and current guidelines recommend cardiac SPECT and fluorodeoxyglucose (FDG) PET for viability assessment. Takotsubo cardiomyopathy (TTC) is a disease characterized by acute but reversible HF leaving no scarring. To explore how robust the semi-quantitative viability criteria used in cardiac SPECT and FDG PET stands their ground in a population with TTC. From 1 September 2009 to 1 October 2012, 24 patients suspected of TTC were enrolled in a multimodality cardiac imaging research project. Echocardiography, (99m)Tc SPECT, and (18)F FDG PET were performed during the acute admission and at follow-up 4 months later. Nineteen patients had a final diagnosis of TTC consistent with Mayo Clinic Diagnostic Criteria. Three of these patients were excluded from further analysis, since wall motion abnormalities were not persistent at the time of nuclear imaging. The remaining sixteen patients exhibited a distinct pattern with HF, "apical ballooning" and a perfusion-metabolism defect in the midventricular/apical region. When viability criteria were applied, they identified significant scarring/limited hibernation in the akinetic part of the left ventricle. However, full recovery was found in all TTC patients on follow-up. Using the current guideline-endorsed viability criteria for semiquantitative cardiac SPECT and FDG PET, these modalities failed to demonstrate the presence of viability in the acute state of TTC.