The authors describe a case of nodular-sclerosing Hodgkin's disease, originally observed in clinical stage III B and treated by systemic chemotherapy, with relapse after a 28-year disease-free interval. As far as we know, the length of remission in this case is second only to that of a case recently described by Hung and co-workers. Therefore, although according to data in the literature relapse after a very long disease-free interval is more frequently observed in patients with stage I A and II A disease, it may occur also in cases with symptomatic, widespread disease. This phenomenon, while reflecting the complexity of relations between the different factors (histologic subtype, clinical stage, host vs tumor defenses, therapy, etc.) that variously affect the clinical course and outcome, underlines the need for cautiousness when assessing the ultimate prognosis of individual cases of Hodgkin's disease.