This study further assesses a previously reported clinicopathologic staging system for colorectal carcinoma. By using carefully defined anatomic criteria, various substages of tumor spread have been examined prospectively for their prognostic significance in a group of 1117 patients accessioned over 14 years and documented by the same pathologist. Spread from the muscularis propria into surrounding tissues was not associated with a significant deterioration in prognosis if the lines of resection were clear of tumor and there were no known metastases or free mesothelial surface invasion. Free mesothelial surface invasion by potentially curable tumors was associated with a significant reduction in patient survival. Patients with potentially curable tumors but with lymph node metastases had a significantly poorer probability of survival if the apical lymph node was involved. Among those with incurable tumors, there was no significant difference in survival depending on whether incurability was due to distant metastases or surgical transection of tumor. Substaging offers a means of refining the ability to predict tumor behavior.