Accurate predictors for metachronous colorectal cancer (CRC) development after polypectomy are lacking. We evaluated the prognostic value of classical clinicopathologic features and a monotonous population of elongated cells (MPECs) in colorectal adenomas from 171 consecutively selected population-based patients with long-term follow-up. Quantitative image analysis, and univariate and multivariate regression analysis were applied. Ten of 171 adenomas (5.8%) developed metachronous CRC (defined as >24 mo interval and >5 cm from the index adenoma to the cancer). Median follow-up of adenomas with metachronous CRC was 68.4 and without cancer 149.7 months (range: 25 to 192 and 25 to 256, respectively). The most prognostic classical features were the localization of the marker adenoma as proximal (ie, in the cecum through transverse colon) versus distal from the transverse colon [P=0.0003, hazard ratio (HR)=8] and the number of polyps found during colonoscopy (2, P=0.002, HR=6). Quantitative features of the MPECs included the longest nuclear axis and variance of the number of nuclei with 2 neighbors (higher and lower in cancer cases, respectively). Of the 171 adenomas, 50 (29%) had MPECs, of which 9 (18%) patients developed metachronous CRC at follow-up, contrasting 1/121 (0.8%) without MPECs (P=0.0003, HR=23). MPECs occurred in both low-grade and high-grade dysplasia, and in tubular and (tubulo) villous adenomas. MPECs had the strongest predictive value for metachronous CRC development. Adenomas proximally located had additional value but only if they were MPEC positive (which only occurred in 5 adenomas, 3 of which (60%) developed cancer). Having more than 2 polyps also had additional prognostic value but only in MPEC-negative adenomas [10 cases; 1 (10%) developed cancer]. Dysplasia grade and histologic growth pattern had no additional value. Thus, colorectal adenomas with subsequent metachronous cancer development can be identified more accurately with MPECs than with classical prognostic factors.