The rearranging antigen receptor genes of lymphoid cells serve as unique clonal markers of lymphoid neoplasms. Gene rearrangement analysis is a highly sensitive and reproducible tool which is useful in the diagnosis and classification of malignant lymphoma/leukemia. Although clonality can often be determined among B cell neoplasms by virtue of immunoglobulin isotype analysis, no such phenotypic marker of clonality exists for T cells. Therefore, clonality of T lymphoproliferative processes is most readily determined by rearrangement analysis of the T cell antigen receptor genes. The alpha, beta, gamma, and delta genes of the T cell receptor gene family encode heterodimeric surface antigen receptors and undergo rearrangement early in T cell differentiation. Identification of rearrangement of T cell antigen receptor genes provides valuable diagnostic information concerning cellular lineage, clonality and classification of T cell neoplasms. This molecular approach is applicable to the diagnosis of occult disease, relapse, and resolution of diagnostic dilemmas in any type of tissue sample including fluids and needle aspirations.