We present a case of a 65 years-old male with sickle cell mutation and beta-thalassemia (Hb S/β-Thal), who had whole-body bone scan evaluation for osteomyelitis. The examination revealed high radiopharmaceutical uptake in the left abdomen. Further evaluation with hybrid single photon emission computed tomography/computed tomography (SPECT/CT) showed calcification of approximately the entire spleen, in the context of sickle cell anemia. This report highlights the role of SPECT/CT in such cases.