By transcriptomic analysis, we identify LEF1 signalling as upregulated in Fbxw7/FBXW7‐mutant mouse and human endometrial cancers, and in human isogenic cell lines carrying FBXW7 mutation, and validate LEF1 and the additional Wnt pathway effector TCF7L2 as novel FBXW7 substrates. This evidence concerns the gene LEF1 and endometrial cancer.