Radiolabeled leukocyte scintigraphy is a well-established technique for the diagnosis of inflammation and infection with a typical presentation of a hot spot within the abnormal areas. However, in some cases of osteomyelitis of the axial skeleton, a cold defect pattern has been described. Tc-99m ciprofloxacin is a new agent claimed to be specific for imaging sites containing viable bacteria. In this report, we present three cases of proved bacterial infection of the axial skeleton with a mismatch pattern between Tc-99m ciprofloxin and tagged leukocytes. Although Tc-99m-labeled leukocyte scanning showed a cold defect, probably caused by bone marrow replacement, the Tc-99m ciprofloxacin consecutively revealed a hot spot at the site of infection. These data suggest that Tc-99m ciprofloxacin should be a better agent than radiolabeled leukocytes for detecting osteomyelitis of the axial skeleton.