OBJECTIVE The diagnosis of cutaneous T-cell lymphoid infiltrates may be difficult based on clinical and routine immunohistologic findings. In this situation, an ancillary technique demonstrating the presence of a monoclonal cell proliferation could help to rule in or out cutaneous T-cell lymphoma (CTCL) in cases that clinically and histopathologically do not allow a definitive diagnosis. Southern blot analysis is a time-consuming method with low sensitivity that should not be considered for the routine diagnosis of cutaneous lymphoid infiltrates. Moreover, it can be used only when fresh tissue is available. New assays based on the amplification of the T-cell receptor gamma (TCR gamma) chain gene rearrangement by polymerase chain reaction (PCR) have been proposed to overcome these limitations. METHODS We retrospectively studied 124 biopsies from 104 patients (66 biopsies with the clinical and histological diagnosis or suspicious of CTCL and 58 biopsies with histological diagnosis of benign reactive dermatological conditions who presented to the Dermatology Unit at King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia between 1996 and 2004. The specimens were morphologically examined and then analyzed by PCR for the gamma chain of the TCR gamma followed by gel electrophoresis. RESULTS The results showed 87.1% sensitivity and 92% specificity in detecting clonal T-cell gene rearrangements among CTCL cases with a positive predictive value of 93.1% and negative predictive value of 85.2%. Therefore, negative TCR gamma results in CTCL should be taken with caution. CONCLUSIONS The detection of clonal TCR gamma gene rearrangement by PCR based method is an adjuvant diagnostic marker for CTCL, although it can be seen in some benign dermatoses.