Abstract: A20 was originally identified as a key regulator of inflammation signalling pathways, a NF-κB inhibitor. Recently, A20 has also been proposed to function as a tumor suppressor. Lacking A20 is involved in tumorigenesis in several human B-cell lymphomas. In this review, current knowledge concerning the feature of A20 biological activities, as well as the underlying molecular mechanisms, and the regulating role of A20 in lymphocytic malignancies is summarized.