Purpose: The present study investigated the utility of whole body positron emission tomography (PET) with 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG) in predicting relapse of malignant lymphoma in patients with residual masses persisting after treatment. Methods: Thirty-six patients with Hodgkin's disease (n = 14) or non-Hodgkin's lymphoma (n = 22) were prospectively enrolled and subjected to 1-4 FDG-PET imaging sessions after completion of therapy. A residual mass had been previously demonstrated in all patients by computed tomography (CT). Sensitivity, specificity, positive and negative predictive value of the method are reported. Tumour-to-normal soft-tissue contrast ratios (TCR) were measured by region of interest (ROI) as a quantitative approach to the evaluation of PET images in patients with positive FDG uptake. Results: Twenty-five of 27 patients with negative FDG-PET after treatment remained in complete remission (CR), and only two patients relapsed. In contrast, of the nine patients with positive scans, four patients retained their CR status, while five showed evidence of relapse. Overall, the sensitivity of FDG-PET was 71%, specificity 86%, negative predictive value 93% and positive predictive value 56%. The probability of relapse-free survival was significantly (P = 0.0057) predicted by a negative FDG-PET. High FDG uptake in the residual tumours was not associated with a high relapse rate (P = 0.117). Conclusion: These studies demonstrate that lack of FDG uptake in residual masses after completion of treatment is associated with a high probability of long-term disease-free survival. Furthermore, when comparing results of FDG-PET imaging with those obtained by CT, our data emphasize that the demonstration of a mass on CT does not necessarily imply the persistence of residual disease.