Follicular lymphoma (FL) typically presents as a systemic disease (stages III/IV). We repeatedly observed in cases with conserved reactive follicle structures (so-called partial infiltration) an association with a limited clinical stage (I/II). In this study, we analyzed 53 lymph node biopsies of FL with conserved reactive follicle structures. In 44 cases (83%) of the patients with partial infiltration, a limited stage of disease (Ann Arbor stage I/II) was found, whereas only 9 of 53 cases (17%) suffered from a systemic disease. In those cases with at least one follicle totally spared by lymphoma, 95% of the patients (38 of 40 cases) presented with a limited stage (I/II) of disease, compared with only 20% (10 of 49 cases) in a control group with full-blown infiltration (P < 0.001). Analyzing systematically all 321 FL cases sent to the Reference Center Würzburg in the year 2001, reactive follicle remnants were detected in 34 of 321 (10.6%) cases with 26 of 34 (76%) tumors showing limited stage (I/II) disease, including all 18 cases with at least one totally spared follicle. Our results therefore show a clear association between the occurrence of preserved reactive follicles in FL and limited disease stage.