Microarray analysis is a promising new approach for creating specific expression profiles of multiple genes simultaneously. We quantitatively analyzed differential gene expression patterns in mycosis fungoides-derived clonal T cells and autologous, identically cultured CD4+ lymphocytes using microarrays containing 588 cDNA segments from genes relevant to cell signaling, carcinogenesis, and apoptosis. Among other dissimilarities, neoplastic T cells showed coexpression of CD40 (Bp50) and CD40 ligand (gp39, CD154). These results could be corroborated by reverse transcription-PCR, immunohistochemistry, and two-color immunofluorescence staining. Our data suggest that in cutaneous T-cell lymphoma, CD40/CD40 ligand interactions might represent a paracrine loop that is crucial not only in preventing apoptosis or positively regulating growth but also in homing of neoplastic cells to the skin.