Coronavirus disease (COVID-19) vaccination is known to cause a diagnostic dilemma due to false-positive findings on [F]FDG PET in vaccine-associated hypermetabolic lymphadenopathy. We present two case reports of women with estrogen-receptor (ER)-positive cancer of the breast who were vaccinated for COVID-19 in the deltoid muscle. [F]FDG positron emission tomography (PET) demonstrated primary breast cancer and multiple axillary lymph nodes with increased [F]FDG uptake, diagnosed as vaccine-associated [F]FDG-avid lymph nodes. Subsequent [F]FES PET revealed single axillary lymph node metastasis in the vaccine-associated [F]FDG-avid lymph nodes. To the best of our knowledge, this is the first study showing the usefulness of [F]FES PET in diagnosing axillary lymph node metastasis in COVID-19-vaccinated patients harboring ER-positive breast cancer. Thus, [F]FES PET has potential applications in the detection of true-positive metastatic lymph nodes in patients with ER-positive breast cancer regardless of the ipsilateral or contralateral side, who have received COVID-19 vaccination.