A 65-year-old woman with a history of ductal mammary carcinoma and recent autonomic dysfunction underwent a Rb-82 chloride (RbCl) cardiac PET/CT scan that showed no ischemia or scarring, but significantly reduced myocardial flow reserve (MFR) (global: 1.5) and a CAC-Score of 0. The patient’s chemotherapy history (paclitaxel, carboplatin, epirubicin, pembrolizumab 2 years before) with elevated Troponin T and NT-pro-BNP levels at that time, and now reduced MFR with 0 CAC suggests cancer-therapy-related cardiotoxicity. An important differential diagnosis to the more common CAD-associated microvascular disease. Furthermore, tumor recurrence with a PET-avid lymph node metastasis was found additionally.