We conducted this study to assess the clinical utility of heteroduplex analysis of polymerase chain reaction (PCR) products for Tgamma gene rearrangements in the diagnosis of T-cell lymphoproliferative disorders (LPDs) using a single set of consensus primers. This method was used to study 103 cases using fresh or frozen tissue. These included 62 cases of T-cell LPDs, 25 cases of B-cell LPDs, 3 cases of anaplastic large cell lymphomas of undefined lineage, and 13 cases of reactive disorders. The latter group served as the negative control group. For all cases of T-cell LPDs, the results of Tbeta Southern analysis (SA) and heteroduplex PCR analysis were compared. We also studied 10 cases of postthymic T-cell lymphoma using paraffin-embedded tissue. Heteroduplex Tgamma PCR was positive in 51 (89%) of 57 cases that were rearranged by Tbeta SA. Eight of the 10 cases of T-cell lymphoma analyzed using paraffin-embedded tissue were positive. There were no false-positive results. These results demonstrate that this method is an effective screening test in the clinical laboratory. A positive result obviates the need to perform SA. Preliminary results suggest this method is useful using paraffin-embedded tissue.