The prognostic value of S-phase fraction (SPF), determined by flow cytometric study from paraffin-embedded tissue, and grading by Working Formulation (WF) and Kiel classification were compared among 245 patients with non-Hodgkin's lymphoma followed for the median of 89 months or until death. Histologic reclassification and SPF determinations were done without knowledge on clinical data. SPF (P equals 0.0001), WF (P equals 0.0003), and Kiel classification (P equals 0.0008) were associated with mortality in lymphoma in a univariate analysis, and WF and SPF were independent prognostic factors in Cox's multivariate analysis. Although SPF correlated strongly both with WF and Kiel grades (P less than 0.0001), low-grade and high-grade malignant lymphomas according to Kiel classification, and high-grade lymphomas according to WF could be divided into groups with significantly different outcome by SPF. The results suggests a role for SPF in therapeutic decision-making.