Distinguishing between Charcot Neuroarthropathy (CN), osteomyelitis (OM), and CN complicated with superimposed OM in diabetic patients is crucial for the treatment choice. Given that current diagnostic methods lack specificity, advanced techniques, e.g., magnetic resonance imaging (MRI) and 99mTc-HMPAO-WBC Single Photon Emission Computed Tomography (SPECT/CT), are needed. This study addresses the challenges in distinguishing OM and CN. We included diabetic patients with CN and soft tissue ulceration. MRI and 99mTc-HMPAO-WBC SPECT/CT were used for the diagnosis. The patients were classified into three probability levels for OM (i.e., Definite, Probable, and Unlikely) according to the Consensus Criteria for Diabetic Foot Osteomyelitis (CC-DFO). Eight patients met the eligibility criteria. MRI, supported by SPECT-CT and CC-DFO, showed consistency with the OM diagnosis in three cases. The key diagnostic features included the location of signal abnormalities and secondary features such as skin ulcers, sinus tracts, and abscesses. Notably, cases with inconclusive MRI were clarified by SPECT/CT, emphasizing its efficacy in challenging scenarios. The primary objective of this study was to compare the results of MRI and 99mTc-HMPAO-WBC SPECT/CT with the CC-DFO score in the diabetic foot with CN and suspected OM. Advanced imaging offers a complementary approach to distinguish between CN and OM. This can help delineate the limits of the disease for presurgical planning. While MRI is valuable, 99mTc-HMPAO-WBC SPECT/CT provides additional clarity, especially in challenging cases or when metallic implants affect MRI accuracy.