BACKGROUND: Cardiac uptake on oncologic FDG PET/CT can be unpredictable. Focal or mass-like cardiac uptake not confined to normal pattern is a real challenge for interpretation due to great variability in physiologic uptake and rarity of either primary or metastatic cardiac neoplasms. METHODS AND RESULTS: Eight patients with suspicious mass-like cardiac uptake on oncologic FDG PET/CT were retrospectively analyzed with correlation to cardiac workups including contrast CT, echocardiography, and repeat PET/CT. Four patients had real cardiac lesions or metastases. Focal uptake was benign and might represent papillary muscle in the other four. SUV ratio between the cardiac focus and surrounding background cardiac uptake was statistically higher in the true-positive group than that in the false-positive group. In addition, the patients with true-positive cardiac uptake had more diffuse distant metastases compared to those with false-positive cardiac uptake. CONCLUSIONS: Focal suspicious cardiac uptake on oncology FDG PET/CT warranted further evaluation. SUV ratio between the cardiac focus and surrounding background cardiac uptake and status of distant metastases might help to differentiate malignant from benign nature of the focal cardiac uptake on FDG PET/CT. Focal uptake of the right ventricle on oncologic FDG PET/CT is more likely suggestive of a neoplasm.