The SENECa study aimed to evaluate the involvement of sentinel lymph nodes (SLNs) in early-stage (FIGO 2009 I–II) endometrial cancer, considering molecular subtypes and the new European Society of Gynaecological Oncology (ESGO) risk classification. The study retrospectively reviewed data from 2139 women across 66 centers in 16 countries, with molecular analysis performed on pre-operative biopsies or hysterectomy specimens. The molecular subgroups included p53 abnormal (p53abn), non-specific molecular profile (NSMP), mismatch repair deficient (MMRd), and POLE mutated (POLE-mut). Tracer diffusion was detected in 97.2% of cases, with bilateral diffusion observed in 82.7%. Ultrastaging or one-step nucleic acid amplification identified 205 patients with affected SLNs, representing 9.6% of the sample. Significant differences in SLN involvement were observed between molecular subtypes, with p53abn and MMRd groups having the highest rates (12.50% and 12.46%, respectively) compared to NSMP (7.80%) and POLE-mut (6.30%). The study also noted significant differences in SLN involvement rates among ESGO risk groups, with high-intermediate and high-risk groups having the highest rates. The findings highlight the importance of considering molecular characteristics for accurate staging and optimal management decisions in early-stage endometrial cancer.The SENECa study aimed to evaluate the involvement of sentinel lymph nodes (SLNs) in early-stage (FIGO 2009 I–II) endometrial cancer, considering molecular subtypes and the new European Society of Gynaecological Oncology (ESGO) risk classification. The study retrospectively reviewed data from 2139 women across 66 centers in 16 countries, with molecular analysis performed on pre-operative biopsies or hysterectomy specimens. The molecular subgroups included p53 abnormal (p53abn), non-specific molecular profile (NSMP), mismatch repair deficient (MMRd), and POLE mutated (POLE-mut). Tracer diffusion was detected in 97.2% of cases, with bilateral diffusion observed in 82.7%. Ultrastaging or one-step nucleic acid amplification identified 205 patients with affected SLNs, representing 9.6% of the sample. Significant differences in SLN involvement were observed between molecular subtypes, with p53abn and MMRd groups having the highest rates (12.50% and 12.46%, respectively) compared to NSMP (7.80%) and POLE-mut (6.30%). The study also noted significant differences in SLN involvement rates among ESGO risk groups, with high-intermediate and high-risk groups having the highest rates. The findings highlight the importance of considering molecular characteristics for accurate staging and optimal management decisions in early-stage endometrial cancer.