Background: Accurate identification of pathological response to neoadjuvant therapy for clinical stage III melanoma before surgery may allow us to better tailor the treatment. RECIST 1.1 has shown poor concordance rates with pathological responses and EORTC FDG-PET/CT response criteria using SUV max is susceptible to internal and external variables leading to difficulty in determining accuracy appropriately. Methods: We conducted a multicenter retrospective analysis of patients with clinical stage III melanoma treated with neoadjuvant nivolumab 3mg/kg + ipilimumab 1mg/kg(N3+I1) for two cycles who did baseline and pre-operative 18F-FDG-PET/CT. RECIST 1.1 and EORTC PETCT criteria were used to classify patients in terms of response. The pathological results were correlated to the image findings. Results: Between Jan 2019 and Jan 2024, 37 patients with clinical stage III melanoma treated with neoadjuvant N3+I1 were identified. Gender: 25 males (67%), median age (years): 58 (range: 31-78), BRAFV600 mut: 25(67%), positive nodes on baseline exam:1=30 (81%), 2=4(11%), and 3 or more =3(8%). Stage AJCC 8th edition: IIIB=23 (62%), IIIC=12 (32%), IIID=2(6%). Among them, 34 had baseline and post-neoadjuvant therapy PET-CT. Twenty-one (62%) had major pathological response (MPR) and 13(38%) had non-MPR. Using objective response and non-objective criteria to capture MPR and non-MPR, respectively, we found the following results: RECIST 1.1 (sensitivity= 48%, specificity=100%, accuracy=68%), EORTC-PET (sensitivity=90%, specificity=69%, accuracy=82%). Combining RECIST 1.1 and EORTC-PET/CT analysis, we found that: double objective responders (CR/PR and CMR/PMR, n=10) had 100% specificity to MPR and double progressors (PD/PMD, n=9) had 95% specificity to non-MPR. The only patient classified as double progressor that did not have non-MPR presented an intense inflammatory response with fever, pain and erythema leading to an increase in the size and number of lymph-nodes. No viable cells were found in the pathological report. Conclusions: Using combined RECIST 1.1 and EORTC-PET/CT response criteria may help to predict pathological response in patients with clinical stage III melanoma who undergo to neoadjuvant nivolumab and ipilimumab.