The usefulness of neutrophil CD64 expression was examined in diagnosing local infection, including soft tissue, bone, and joint infections. Among 99 patients suspected of local infection, 31 were confirmed and 68 patients were not. The CD64 level of patients with local infection was significantly higher than in those without infection [4,193 ± 1,132 vs. 1,017 ± 59 molecules/cell (mean ± standard deviation); p < 0.001]. The area under the curve of CD64 calculated by receiver operating characteristic curve analysis was larger than that of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), or white blood cell (WBC) count. In addition, CD64 levels of patients with crystal-induced arthritis remained within cutoff value (2,000 molecules/cell). These data suggest that measuring CD64 expression can be a useful diagnostic marker for local musculoskeletal infection and crystal-induced arthritis.