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Osteomyelitis often complicates a diabetic neuropathic foot, leading to amputation, decreased function, and quality of life. Therefore, early detection and treatment are paramount. Furthermore, neuroarthropathic (Charcot) changes in the foot often resemble infection and must be differentiated. Currently, the Tc-99m HMPAO Labeled Leukocytes Scan is considered to be the most reliable noninvasive imaging modality of choice in determining Charcot foot changes versus osteomyelitis. The purpose of this article is to alert the clinician that although the Tc-99m HMPAO Labeled Leukocytes Scan may be the second most reliable test next to bone biopsy for determining osteomyelitis, false positives do occur. (J Am Podiatr Med Assoc 91(7): 365-368, 2001)