Myometrial invasion with a microcystic, elongated, fragmented (MELF) pattern is a unique histologic characteristic rarely seen in low-grade endometrial carcinomas (EC). Due to contradictory results and a lack of relevant research within the context of the molecular EC categorization, the prognostic significance of MELF invasion was unclear. Researchers’ study objectives were to characterize the predictive significance of MELF invasion in early-stage low/intermediate risk EC and to determine the relationship between MELF invasion and clinicopathological and molecular features. The 1,141 women with (high) intermediate-risk EC who participated in the PORTEC-1/2 studies evaluated single complete tumor slides in 979 cases (85.7%). Similarities and differences in clinicopathological and molecular characteristics were examined between MELF invasion-positive and -negative patients. The Kaplan-Meier method, log-rank tests, and Cox’s proportional hazards models were utilized to conduct the time-to-event studies. Grade 1-2 histology, extensive invasion into the lymph-vascular space invasion (LVSI), and deep myometrial invasion were all related to the presence of MELF in 128 (13.1%) patients. Tumors with a positive MELF invasion score were NSMP EC in 85.6% of cases. CTNNB1 wild type was found in 92.2% of NSMP EC with MELF invasion, and KRAS mutations were found in 24.4% of NSMP EC. Those with a positive MELF invasion score had a lower risk of recurrence than those with a negative score (4.9% vs. 12.7%, P=0.026). After considering other clinicopathological and molecular variables, the probability of recurrence was not affected by MELF invasion (HR 0.65, P=0.30).