Recent evidence suggests that endoscopic submucosal dissection alone is sufficient for treating patients with T1 colorectal cancer (CRC) who are at low risk for developing lymph node metastasis (LNM); whereas more extensive radical surgery (RS) is needed only for high-risk patients. Unfortunately the current risk-stratification criteria based on the postendoscopic pathological examination, which includes positive surgical margins, poor tumor differentiation, presence of vascular or lymphatic invasion, depth of submucosal invasion (>1000 μm) and high-grade tumor budding; tend to overestimate the degree of risk, and inadvertently categorize >70 to 80% of T1 CRCs into the high-risk category. However, in reality, based on postsurgical pathology results, only 8% to 16% of all patients with T1 CRC are truly LNM-positive, and most of them unnecessarily undergo RS procedures. This is a significant clinical challenge, as these surgeries are expensive and associated with various complications, including higher mortality rates. We previously reported a microRNA (miRNA) signature that allowed robust detection of high-risk patients with T1 CRC. Although recent evidence has highlighted the importance of gene expression in stratifying patients with CRC into distinct consensus molecular subtypes, no studies have yet undertaken a comprehensive effort to identify gene expression signatures for the detection of LNM in patients with T1 CRC.