Differentiation between cutaneous pseudo-T-cell lymphomas and cutaneous T-cell lymphomas (CTCLs) may be extremely difficult. In this study, it was investigated whether demonstration of an aberrant phenotype and detection of clonal T-cell receptor gamma (TCR gamma) gene rearrangements can be used as additional differential diagnostic criteria. Immunohistochemical studies and TCR gamma gene rearrangement analysis using a polymerase chain reaction with primers specific for V gamma 1-8 and V gamma 9 gene segments in combination with denaturing gradient gel electrophoresis (PCR/ DGGE) were performed on frozen material of 11 pseudo-T-cell lymphomas and 17 CTCLs, including 9 cases of mycosis fungoides (MF) and 8 pleomorphic CTCLs. Clonal TCR gamma gene rearrangements were found in 66% of patch/plaque-stage MF and 100% of tumor-stage MF and pleomorphic CTCL, but not in any of 10 pseudo-T-cell lymphomas studied. Aberrant expression of CD2, CD3, and/or CD5 antigens was noted in 3 of 6 (50%) cases of patch/plaque-stage MF, all three cases of tumor-stage MF, and 5 of 8 (62%) pleomorphic CTCLs, but not in any of the 11 pseudo-T-cell lymphomas. Moreover, in pseudo-T-cell lymphomas exhibiting a nodular or diffuse growth pattern, a considerable admixture with reactive CD8+ T cells (15 to 60%), B cells (up to 20%), and macrophages was a characteristic finding. In conclusion, the results of this study suggest that demonstration of clonal TCR gene rearrangements and an aberrant phenotype, as well as demonstration of many admixed CD8+ T cells and B cells can be considered as useful additional criteria in the differentiation between pseudo-T-cell lymphomas and CTCLs.