ZAP70 (Zeta-chain associated protein kinase) is a 70 kDa member of the SYK tyrosine kinase family. It plays a central role in lymphocyte activation and development, implicated in several immune disorders. ZAP70 controls TCR (T-cell antigen receptor)-linked signal transduction pathways. Its key role in thymocytes development and mature T lymphocytes activation has been illustrated by the characterization of several human immunodeficiencies presenting with mutations in the ZAP70 gene. ZAP70 is also expressed in several types of B-cell neoplasm and is easily detected by immunohistochemistry, providing a useful prognostic marker in patients with chronic lymphocytic leukaemia.