The authors' previous study showed the presence of follicular dendritic cell (FDC) networks--though altered--in neoplastic areas, not only in the nodular lymphocyte predominance type, but also in other types of Hodgkin's disease. The present retrospective study was performed on 102 patients to determine whether the presence or absence of FDC networks, or parts of them, in neoplastic areas has prognostic relevance in Hodgkin's disease. Follicular dendritic cells were visualized with the monoclonal antibody Ki-FDC1P, which selectively stains FDCs in paraffin-embedded tissues. Univariate statistical analysis, in which nodular sclerosis (NS) and mixed cellularity (MC) types were combined, showed three prognostically different groups: the best prognosis was associated with nodular lymphocyte predominance cases; the worst with FDC-negative NS or MC cases; and an intermediate prognosis with FDC-positive NS or MC cases. In the NS group, the prognosis of FDC-positive cases was better than that of FDC-negative cases. After multivariate analysis, stepwise modeling identified three prognostic factors at diagnosis: stage (P = .001), FDC status (P = .001), and age (P = .06). The authors conclude that in the most common types of Hodgkin's disease (nodular lymphocyte predominance, NS, and MC), FDC status in the neoplastic area(s) bears prognostic relevance, a positive FDC status predicting a favorable prognosis and a negative FDC status an unfavorable one.