CD27 (TNFRSF7) is a member of the TNFR family. It is a type I membrane glycoprotein with a MW of 55KDa that forms a disulfide-linked homodimer. The receptor possesses three cysteine rich repeats in the extracellular domain, the transmembrane region, and the intracellular domain. CD27 binds CD27L (CD70), another member of the TNF ligand family that forms a trimer; thus, it has been speculated that the CD27L binds to a trimeric structure composed by three dimeric CD27 molecules. The interaction between CD27 and its ligand, CD70, plays a role in providing co-stimulation for prolonged lymphocyte survival, enhanced T-cell proliferation, and memory-cell formation. T cells expressing CD27 and CD70 play a key role in regulating B-cell activation and immunoglobulin synthesis. Soluble CD27 (sCD27), the extracellular domain of membrane-bound CD27, can be released after lymphocyte activation by differential splicing of the receptor protein or shedding from the cell surface by metalloproteinases (MMPs). Soluble CD27 has been detected in serum, plasma, and urine samples from healthy individuals, and it has been described elevated sCD27 levels in serum of patients with systemic lupus erythematosus, viral infections, and lymphoid malignancies. The sCD27-pool in cancer patients can be significantly enlarged by immunotherapy. CD27 is recognized as a marker for memory B cells and is considered of diagnostic value in patients who have decreased numbers of switched memory B cells.