Background Ultrastructural and immunohistochemical differences have been described in FDCs of primary and secondary follicles, illustrating the highly compartmentalized structure of lymph follicles. Differences in FDC immunophenotype in different grades of FL may reflect some parallelism between reactive and neoplastic conditions in terms of FDC-B cell interaction and may be used as a valuable additional tool for grading FL. Methods A total of 60 paraffin blocks from patients with follicular lymphoma, 30 cases each of grade 1 and 3, were retrieved from our archive. Immunohistochemical analysis was carried out for CD21, CD23, cyclin A, and Ki-67. Results Our study demonstrates that during evaluation, six patterns of FDC distribution were distinguished. The intensity of stain for CD21 was not statistically significant in grade 1 and grade 3 FL ( p = 0.340). In contrast, grade 3 FLs exhibited a significant decrease of CD23 expression by the FDCs ( p < 0.001). By CD21 stain, there was no significant difference in the distribution of pattern 1 in grades 1 and 3 ( p = 0.098). In contrast, in grade 3, this pattern was significantly less observed by CD23 stain ( p = 0.016). The same was observed for pattern 2 for CD21 ( p = 0.940) and CD23 ( p = 0.010) and pattern 4 for CD21 ( p = 0.305) and CD23 ( p = 0.005), respectively. Distribution of pattern 5 was significantly different between grades 1 and 3 both for CD21 ( p = 0.005) and CD23 ( p < 0.001). Distribution of patterns 2 and 6 was not significantly different between grades 1 and 3 for CD21 and CD23. The values of cyclin A and Mib-1 were also significantly different between grades 1 and 3 ( p < 0.001). Conclusions The observed patterns of FDCs lead us to believe that similar to reactive lymph node follicles, neoplastic follicles in FL, at least in early stages, have an organized structure. Hypothetically, with CD21, CD23, and cyclin A immunohistochemistry, the sequence of events in FL progression may be traced.