Terminal deoxynucleotidyl transferase (TdT) is an unusual deoxynucleotide polymerizing enzyme with a molecular weight of about 58 kDa found normally only in B- and T-cell lymphoblasts/prelymphocytes. TdT generates antigen receptor diversity by synthesizing non-germ line elements (N-regions) at the junctions of rearranged Ig heavy chain and T cell receptor gene segments. Rare TdT-positive cells are regularly detected in thymus and bone marrow. Typically, TdT expression in the thymus is very variable from cell to cell since it is rapidly decreased in more mature T-cells. TdT-positive cells may occasionally be found in tonsils, lymph nodes and extranodal lymphoid tissue. Immunohistochemical detection of TdT has value in classification of malignant lymphomas and acute leukemias, particularly for the identification of pre-B and pre-T acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL).