The prognostic value of S-phase fraction (SPF) determined by flow cytometry from a fine-needle aspirate was investigated in a prospective series of 52 non-Hodgkin lymphomas. The aspirates were drawn either at diagnosis (n = 16) or at lymphoma recurrence (n = 36). Patients with lymphoma with a large SPF (> 10%, n = 24) had only a 21% 3-year survival rate corrected for intercurrent deaths as calculated from the date of aspiration, whereas a smaller SPF was associated with a 71% 3-year survival rate (n = 28, P = 0.0009). SPF size also correlated with Working Formulation grading (P = 0.002). In a multivariate analysis the relative risk of death from lymphomas with a large SPF was 4.01 (1.60-10.1), whereas histological grading, age, and sex had no additional independent prognostic value. SPF determined from a fine needle aspirate had unexpectedly good prognostic value, and the result suggests that the method is of clinical importance.