Cluster of differentiation 163 (CD163) is an acute phase-regulated receptor involved in the clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages, thereby protecting tissues from free hemoglobin-mediated oxidative damage. Expression of CD163 is restricted to cells of the monocyte/macrophage lineage. The solubilized form in plasma is upregulated in inflammatory diseases such as rheumatoid arthritis, atherosclerosis, and Gaucher's disease, which coincides with recent studies that have found IL-10, glucocorticoids, and other inflammatory modulators to upregulate CD163 expression. CD163 staining is useful for differentiating synovial intimal fibroblasts from synovial macrophages in rheumatoid arthritis. Overexpression of CD163 is also present in patients with myelomonocytic leukemia dealing with microbial infections. CD163 expression is found in leukemias with monocytic differentiation, and synovial-type giant cell tumors of the vertebral column.