Chronic lymphocytic leukemia (CLL) is a disease with variable clinical course. ZAP-70 expression shows a high concordance with IgVH gene mutational status and the method of detection for ZAP-70 expression is relatively simple, thus the ZAP-70 is used as a surrogate marker for IgVH gene mutational status. In recent years, ZAP-70 expression evaluation of different methods have shown difference that restrict the clinical application of ZAP-70. Therefore, the standardization of ZAP-70 expression detection has become a focus. The current review summarizes bio-characteristics, clinical application and detection method of ZAP-70. The detection methods of ZAP-70 are divided into analytical methods and experiment techniques. The analytical methods include percentage method, fluorescent quantitation and ratio method, in which the most important procedure is setting control. The experiment techniques include sample storage, time from blood draw to detection, fixation method, the antibody and the selection of fluorescence. Plenty of literatures have compared the variables, but the standardization of ZAP-70 expression detection method has not yet been decided.