Although positron emission tomography (PET) imaging is now recognized as a useful tool for staging intermediate and high-grade non-Hodgkin's lymphoma (NHL), few data are available regarding its accuracy in low grade NHL. We therefore studied 36 patients with histologically proven low-grade NHL. Whole-body 2-(fluorine-18) fluoro-2-deoxy-D-glucose (FDG) PET was performed at the time of initial diagnosis (n = 21) or for disease recurrence (n = 15) prior to any treatment. PET results were compared to those of physical examination and computed tomography (CT). PET studies were read without knowledge of any clinical data. Any focus of increased activity was described and given a probability of malignancy using a 5 point-scale (0: normal to 4: definitively malignant). An individual biopsy was available for a total of 31 lesions. The sensitivity and specificity were 87% and 100% for FDG-PET, 100% and 100% for physical examination and 90% and 100% for CT respectively. In addition, 42 of 97 peripheral lymph node lesions observed by FDG-PET were clinically undetected, whereas the physical examination detected 23 additional nodal lesions. PET and CT both indicated 12 extranodal lymphomatous localizations. FDG-PET showed 7 additional extranodal lesions while 5 additional unconfirmed lesions were observed on CT. Regarding bone marrow infiltration, PET and biopsy were concordant in 24 patients with 11 true positive (TP) and 13 true negative (TN). However PET was FN in 11 patients and no biopsy was performed in one patient. The combination PET/CT/physical examination seems to be more sensitive than the conventional approach for staging low grade NHL. Its sensitivity however is unacceptably low for diagnosing bone marrow infiltration.