¹⁸ F-FDG PET/CT is a powerful diagnostic tool in breast cancer (BC). However, it might have a reduced sensitivity in differentiated, oestrogen receptor-positive (ER+) BC. In this setting, specific molecular imaging with fluorine-oestradiol ( ¹⁸ F-FES) PET/CT could help in overcoming these limitations; however, the literature on the diagnostic accuracy of this method is limited. We therefore planned this systematic review and meta-analysis to compare ¹⁸ F-FDG and ¹⁸ F-FES PET/CT in ER+ BC patients. We performed a literature search to identify all studies performing a head-to-head comparison between the two methods; we excluded review articles, preclinical studies, case reports and small case series. Finally, seven studies were identified (overall: 171 patients; range: 7-49 patients). A patients-based analysis (PBA) showed that ¹⁸ F-FDG and ¹⁸ F-FES PET/CT had a similar high pooled sensitivity (97% and 94%, respectively) at the lesion-based analysis (LBA), ¹⁸ F-FES performed slightly better than ¹⁸ F-FDG (pooled sensitivity: 95% vs. 85%, respectively). Moreover, when we considered only the studies dealing with the restaging setting (n = 3), this difference in sensitivity was even more marked (98% vs. 81%, respectively). In conclusion, both tracers feature an excellent sensitivity in ER+ BC; however, ¹⁸ F-FES PET/CT could be preferred in the restaging setting.