AbstractThis study aimed to evaluate the diagnostic accuracy of Node Reporting and Data System (Node-RADS) in discriminating between normal, reactive, and metastatic axillary LNs in patients with melanoma who underwent SARS-CoV-2 vaccination. Patients with proven melanoma who underwent a 2-[¹⁸F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[¹⁸F]-FDG PET/CT) between February and April 2021 were included in this retrospective study. Primary melanoma site, vaccination status, injection site, and 2-[¹⁸F]-FDG PET/CT were used to classify axillary LNs into normal, inflammatory, and metastatic (combined classification). An adapted Node-RADS classification (A-Node-RADS) was generated based on LN anatomical characteristics on low-dose CT images and compared to the combined classification. 108 patients were included in the study (54 vaccinated). HALNs were detected in 42 patients (32.8%), of whom 97.6% were vaccinated. 172 LNs were classified as normal, 30 as inflammatory, and 14 as metastatic using the combined classification. 152, 22, 29, 12, and 1 LNs were classified A-Node-RADS 1, 2, 3, 4, and 5, respectively. Hence, 174, 29, and 13 LNs were deemed benign, equivocal, and metastatic. The concordance between the classifications was very good (Cohen’s k: 0.91, CI 0.86–0.95; p-value < 0.0001). A-Node-RADS can assist the classification of axillary LNs in melanoma patients who underwent 2-[¹⁸F]-FDG PET/CT and SARS-CoV-2 vaccination.