Tuesday, 11 September 2012, 17.00-19. Objective: The most widely used system for histological grading of colorectal cancer (CRC) is based on the degree of gland formation, despite significant interobserver variability and low prognostic value. Herein we analyzed the prognostic significance of a grading system based on the presence of poorly differentiated clusters in stage I CRC. Method: Poorly differentiated cancer clusters were assessed by two independent pathologists in stage I CRC characterized or not by disease progression. Tumors with <5, 5 to 9, and >10 clusters were classified as G1, G2, and G3, respectively. The prognostic value on disease-free survival and the association with other clinicopathologic characteristics of the conventional and novel grading systems were analyzed. Results: K statistics for inter-observer variability in the assessment of histological grade based on poorly differentiated custers was 0.728 (good). High histological grade assessed with the novel system, but not with the traditional one, represented a negative significant prognostic factor for disease-free survival and it was significantly associated with venous invasion, lymphatic invasion, budding, invasive growth and nodal micrometastases. Conclusion: We suggest that a tumor grading system based on the number of poorly differentiated clusters has a stronger power to stratify stage I CRC patients by prognostic outcome than conventional grading.