The authors report two cases of non-Hodgkin's lymphoma that were evaluated not only by conventional staging work-up but also additional Tc-99m MDP bone scans and fluorine-18 fluorodeoxyglucose (F-18 FDG) coincidence detection (CoDe) positron emission tomographic (PET) imaging. There were discordant results between the Tc-99m MDP bone scans and F-18 FDG CoDe PET. In the first case, the bone marrow biopsy was positive, and F-18 FDG CoDe PET was consistent with a malignancy, but the findings of the Tc-99m MDP bone scintiscan were negative. In the second case, the bone marrow biopsy was negative, but F-18 FDG CoDe PET revealed focal skeletal involvement, which improved markedly on the follow-up study after chemotherapy. If skeletal involvement has a focal distribution and is confined to the marrow cavity, both bone marrow biopsy and bone scintigraphy can be falsely negative. In this situation, F-18 FDG PET is useful and revealing.