Background: Staging of Hodgkin's disease (HD) is accomplished by a variety of invasive and non-invasive modalities. This prospective study was undertaken to investigate the value of whole-body positron emission tomography (PET) with 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG) in defining regions involved by lymphoma compared with conventional staging methods in patients with HD. Patients and methods: Fourty-four newly diagnosed patients with HD underwent FDG-PET as part of their initial staging work-up, PET findings were correlated with findings of conventional staging including computed tomography, ultrasound, bone scanning, bone marrow biopsy, liver biopsy and laparotomy. When results of FDG-PET differed to those obtained by conventional methods reevaluation was performed by biopsy, if possible, or magnetic resonance imaging. Results: The results of FDG-PET were compared with three hundred twenty-one conventional staging procedures performed in 44 patients. FDG-PET was positive in 38 of 44 (86%) patients at sites of documented disease. PET detected additional lesions in five cases previously not identified by conventional staging methods. In another case a nodal lesion suspect on CT was negative at FDG-PET and was settled as true negative by biopsy. As a consequence of PET findings five patients had to be upstaged and one patient had to be down-staged, resulting in changes in treatment strategy in all six cases (14%). FDG-PET failed to visualize sites of HD in four patients. In two of our patients a false positive PET result was obtained. Conclusions: Our data indicate that FDG-PET provides an imaging technique that appears to visualize involved lesions in most patients with HD and is useful in the management of these patients.