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Histologic grading has been used as a guide for clinical management in follicular lymphoma (FL). Proliferation index (PI) of FL generally correlates with tumor grade; however, in cases of discordance, it is not clear whether histologic grade or PI correlates with clinical aggressiveness. To objectively evaluate these cases, we determined PI by Ki-67 immunostaining in 142 cases of FL (48 grade 1, 71 grade 2, and 23 grade 3). A total of 24 cases FL with low histologic grade but high PI (LG-HPI) were identified, a frequency of 18%. On histologic examination, LG-HPI FL often exhibited blastoid features. Patients with LG-HPI FL had inferior disease-specific survival but a higher 5-year disease-free rate than low-grade FL with concordantly low PI (LG-LPI). However, transformation to diffuse large B-cell lymphoma was uncommon in LG-HPI cases (1 of 19; 5%) as compared with LG-LPI cases (27 of 74; 36%). In conclusion, LG-HPI FL appears to be a subgroup of FL with clinical behavior more akin to grade 3 FL. We propose that these LG-HPI FL cases should be classified separately from cases of low histologic grade FL with concordantly low PI.