A residual mass after treatment of lymphoma is a clinical challenge, because it may represent vital tumor as well as tissue fibrosis. Metabolic imaging by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) offers the advantage of functional tissue characterization that is largely independent of morphologic criteria. We compared 18F-FDG PET to computed tomography (CT) in the posttreatment evaluation of 54 patients with Hodgkin's disease (HD) or intermediate/high-grade non-Hodgkin's lymphoma (NHL). Residual masses on CT were observed in 13 of 19 patients with HD and 11 of 35 patients with NHL. Five of 24 patients with residual masses on CT versus 1 of 30 patients without residual masses presented a positive 18F-FDG PET study. Relapse occurred in all 6 patients (100%) with a positive 18F-FDG PET, 5 of 19 patients (26%) with residual masses on CT but negative 18F-FDG PET, and 3 of 29 patients (10%) with negative CT scan and 18F-FDG PET studies (P </=.0001). We observed a higher relapse and death rate in patients with residual masses at CT compared with patients without residual masses at CT (progression-free survival at 1 year: 62 +/- 10 v 88 +/- 7%, P =. 0045; overall survival at 1 year: 77 +/- 5 v 95 +/- 5%, P =.0038). A positive 18F-FDG PET study was even more consistently associated with poorer survival: compared with patients with a negative 18F-FDG PET study, the 1-year progression-free survival was 0% versus 86% +/- 5% (P <.0001) and the 1-year overall survival was 50% +/- 20% versus 92% +/- 4% (P <.0001). The detection of vital tumor by 18F-FDG PET after the end of treatment has a higher predictive value for relapse than classical CT scan imaging (positive predictive value: 100% v 42%). This could help identify patients requiring intensification immediately after completion of chemotherapy. However, 18F-FDG PET mainly predicts for early progression but cannot exclude the presence of minimal residual disease, possibly leading to a later relapse.