Background: Early stages of cutaneous T-cell lymphoma (CTCL) may be difficult to distinguish from benign inflammatory dermatoses by routine histologic examination. Objective: Our purpose was to determine whether clonal rearrangements of the T-cell receptor (TCR) g gene by polymerase chain reaction and denaturing gradient gel electrophoresis (PCR/DGGE) could be detected in the early stages of CTCL and to correlate these findings with conventional histopathology. Methods: A total of 39 specimens from 12 patients with CTCL were obtained. The slides were evaluated independently by three dermatopathologists, and categorized into three groups: nondiagnostic, suggestive of CTCL, and diagnostic of CTCL. Of the 39 specimens, 33 were tested by PCR/DGGE by means of GC-clamped primers for clonal rearrangement of the TCR γ gene. Results: The histologic evaluation of the 12 cases showed a significant variation among the three dermatopathologists. The correlation of PCR/DGGE with routine histology was as follows: Clonal TCR γ gene rearrangements were demonstrated in 73% of the specimens nondiagnostic for CTCL, 71% of those suggestive of CTCL, and 74% of those diagnostic of CTCL. Conclusion: Clonal TCR γ gene rearrangements may be detected in patients with early CTCL, even when the histologic findings are not unequivocally diagnostic. In patients with multiple biopsy specimens, identical clones were demonstrated in all rearranged samples, indicating the same neoplastic clone was present in the earliest stages of disease.(J Am Acad Dermatol 1998;38:453-60.)