The biology of colorectal cancer differs according to location within the large intestine. To evaluate the clinical significance of tumor location as a risk factor for lymph node metastasis (LNM), we performed a detailed pathological review of T1 adenocarcinomas of the colon and rectum. T1 adenocarcinomas of the colon and rectum treated by radical resection (n=428) were identified from prospective clinical databases at two institutions. Tumor location was assigned as right colon (cecum to transverse), left colon (splenic flexure to sigmoid), or rectum (0-18 cm from AV). Pathology slides were reviewed, extent of submucosal invasion (sm width, sm depth) was quantified using an optical micrometer, and morphologic features of the cancer and its infiltrating margin were recorded. The overall rate of LNM was 10%. On univariate analysis, LNM was significantly more common in the rectum (27/176, 15%) compared to the left colon (13/160, 8%, p=.04) or right colon (3/92, 3%, p=.003). However, on multivariate analysis, deep submucosal invasion and lymphovascular invasion were independent and significant risk factors, whereas tumor location was not. T1 colorectal cancers have a progressively higher risk of LNM as their location becomes more distal. However, the increasing rate of LNM observed in cancers of the left colon and rectum is explained by a higher prevalence of high-risk pathologic features. In early colorectal cancers, tumor morphology is the strongest clinical predictor of metastatic behavior.