We report a case of polyostotic Paget's disease of bone that caused an unusual pattern of accumulation of 111In leukocytes that mimicked, at some sites, uptake of osteomyelitis, which was suspected in this patient. Technetium-99-m sulfur colloid scan clarified the nature of 111In-leukocyte accumulation as secondary to expanded active bone marrow uptake in some pagetic bones. Additionally, a spectrum of 111In-leukocyte and 99mTc-sulfur colloid uptake was noted in the bones involved by the disease that represented uptake by pagetic foci at different pathologic phases of disease. This case suggests that Paget's disease should be considered as a diagnostic possibility for areas of 111In-leukocyte accumulation, particularly when expanded uptake is seen. When suspected, correlation with bone marrow scan and/or standard radiographs should be obtained. Recognizing that Paget's disease can not only cause absent but also expanded bone marrow (depending on the disease stage) and consequently abnormal 111In-leukocyte uptake, should help avoid interpretational confusion.