The distinction between mycosis fungoides (MF) and inflammatory dermatoses (ID) by clinicopathologic criteria can be challenging. There is limited information regarding the performance characteristics and utility of TCRG and TCRB clonality assays in diagnosis of MF and ID from paraffin-embedded tissue sections. In this study , PCR tests were performed with both TCRG and TCRB BIOMED-2 clonality methods followed by capillary electrophoresis and Genescan analysis using DNA samples from 35 MF and 96 ID patients with 69 and 133 paraffin-embedded specimens , respectively. Performance characteristics were determined for each test individually and in combination. TCRG and TCRB tests demonstrated identical sensitivity (64%) and specificity (84%) when analyzed as individual assays. The positive predictive value, negative predictive value , and change of posttest MF probability over a range of MF pretest probabilities were obtained. These data were used to construct an algorithm for sequential use of TCRG and TCRB. Mycosis fungoides (MF) is the principle form of cutaneous T-cell lymphoma and accounts for nearly 50% of all primary cutaneous lymphomas.1 In a proportion of cases, especially during the early stages, it is difficult to distinguish MF from some reactive inflammatory dermatoses (ID) clinically and histopathologically, and thus a definitive diagnosis is often preceded by a variably long period. Based on the fact that the tumor cells of lymphomas harbor identically (clonally) rearranged T-cell receptor genes whereas reactive skin disorders consist of cells with polyclonal T-cell receptor genes, 2 T-cell receptor clonality testing is commonly performed on cases of suspected MF as an ancillary study to provide additional evidence for diagnosis.The BIOMED-2 collaborative study developed multiplex PCR assays for the detection of clonally rearranged TCR genes, which make interlaboratory comparison possible. Because of the restricted repertoire of V and J segments of TCRG locus and the existence of TCRG recombination in both TCR␥␦ and TCR␣ clonal T-cell proliferations as a result of the chronological order of TCR gene rearrangements in T-cell progenitors, 3 PCR clonality assay of TCRG is the test most often performed in most clinical diagnostic laboratories.The BIOMED-2 group reported an 89% rearrangement rate of the TCRG gene and 94% of the TCRB gene in T-cell malignancies in 2003. 4 In 2006, Morgan et al used the BIOMED-2 PCR primers to examine 10 early-stage MF cases and 10 late-stage MF or Sezary syndrome cases with either fresh or paraffin-embedded tissue specimens. They reported a high frequency of clonally rearranged TCRG (17/20) and TCRB (15/20) genes.5 However, the currently available data on the sensitivity and specificity of BIOMED-2 TCRB clonality assay in testing paraffin-embedded skin tissue of MF is limited and from small datasets.Rigorous test performance assessment is required to determine the utility of clonality testing in skin biopsies. Monoclonality is occasionally found in some benign cutaneous lym...