Radionuclide imaging with technetium-99m phosphate compounds was performed in 18 patients with deep-seated soft-tissue masses. The histologically established diagnosis was intra- or intermuscular lipoma in 13 patients and liposarcoma in five. Radionuclide scans demonstrated disparate scintigraphic characteristics in these two often clinically similar lesions. Soft-tissue radionuclide accumulation occurred in two lipomas and corresponded to radiographically evident calcification. All liposarcomas were uncalcified and demonstrated intense radionuclide activity. This activity may be related to the angiographic and histologic hypervascularity of liposarcomas, which is also demonstrable on computed tomography as contrast enhancement; hence, these modalities offer the same nonspecific diagnostic information. It is concluded, however, that plain radiography and radionuclide scaning should suffice to establish the diagnosis of lipoma.