Background: The determination of clonality has proven to be a useful adjunct to the diagnosis of cutaneous lymphocytic infiltrates. It is considered particularly helpful for the distinction of mycosis fungoides (MF) and inflammatory dermatoses. Objectives: To verify the sensitivity of the polymerase chain reaction (PCR)-hetero-duplex analysis of T-cell receptor γ-chain gene (TCRγ) rearrangements in patients with MF and to establish whether a clinicopathological re-evaluation of lesions previously unclassified or considered to be non-neoplastic entities but found to be monoclonal allowed the recognition of additional cases of MF. Methods: Included in the study were 116 patients, seen at our Institute from April 2002 to September 2003 and tested for TCRγrearrangements. Thirty-six patients were affected by clinically and histopathologically provenMF, while the remaining 80 cases had not been classified or had been classified as non-neoplastic entities. The sensitivity of the molecular analysis was determined on the basis of the results obtained in the 36 patients with MF. The 29 cases of the second series of patients found to be monoclonal were clinically and histopathologically re-evaluated. Results: Clonal rearrangements were found in 87.5%of patients with plaque stage MF and in 20%of those with patch stage MF. The clinicopathological re-evaluation allowed us to reclassify 15 of 29 monoclonal cases of the second series of patients as MF. Conclusions: The study showed that the PCR-hetero duplex technique can determine a high percentage of monoclonality only in plaque stage MF. However, in spite of the low sensitivity of the method, several cases previously unrecognized could be reclassified as MF when their clinical and histopathological features were reevaluated taking into account the clonality of the lymphocytic infiltrate. Background: The determination of clonality has proven to be a useful adjunct to the diagnosis of cutaneous lymphocytic infiltrates. It is considered especially helpful for the distinction of mycosis fungoides (MF) and inflammatory dermatoses. Objectives: To verify the sensitivity of the polymerase chain reaction (PCR) -hetero-duplex analysis of T-cell receptor γ-chain gene (TCRγ) rearrangements in patients with MF and to establish whether a clinicopathological re-evaluation of patients with uncovecified or be to non-neoplastic entities but found to be monoclonal allowed the recognition of additional cases of MF. Methods: Included in the study were 116 patients, seen at our Institute from April 2002 to September 2003 and tested for TCRγrearrangements. Thirty-six patients were affected by clinically and histopathologically proven MF, while the remaining 80 cases had not been classified or had been classified as non-neoplastic entities. The sensitivity of the molecular analysis was determined on the basis of the results obtained in the 36 patients with MF. The 29 cases of the second series of patients found to be monoclonal were clinically and histopathologically re-evaluated. Results: Clonal rearrangements were found in 87.5% of patients with plaque stage MF and in 20% of those with patch stage MF. The clinicopathological re-evaluation allowed us to reclassify 15 of 29 monoclonal cases of the second series of patients as MF. Conclusions: The study showed that the PCR-hetero duplex technique can However, in spite of the low sensitivity of the method, several cases previously unrecognized could be reclassified as MF when their clinical and histopathological features were reevaluated taking into account the clonality of the lymphocytic infiltrate .