T-cell receptor-gamma gene rearrangements provide specific clonal markers for a variety of lymphoid malignancies. T-cell receptor gene rearrangements in patients with cutaneous T-cell lymphoma were examined using conventional Southern blot analysis and a newly developed polymerase chain reaction (PCR)-based technique. The oligoprimers amplified a rearranged V gamma and J gamma segment (including the N region) of the T-cell receptor-gamma gene, and products were resolved using high-resolution nondenaturing polyacrylamide gel electrophoresis. Our results demonstrated concordance between the two techniques in 10 patients with cutaneous T-cell lymphomas (including nine cases of C beta and one case of delta 2 TCR gene rearrangements) and 10 negative controls. In the present study, we have shown that this PCR-based method provides a highly sensitive, specific technique for the detection of T-cell clones of both the alpha beta and gamma delta varieties and could be used in both fresh and formalin-fixed, paraffin-embedded tissues. It is estimated that this PCR-based technique is 10 to 50 times more sensitive than conventional Southern blot analysis in the detection of small T-cell clones.