Comparative hybridization of cDNA arrays is a powerful high-throughput tool for the measurement of gene expression between two or more tissues. Moreover, cDNA array technology permits detection of genes involved in carcinogenesis and prospective targets for diagnosis or therapy in the future. We used this technique in cell lines to discover genes possibly involved in the pathogenesis of the large-cell anaplastic lymphoma (ALCL). CD30(+) lymphoma cells are characteristic for this lymphoma entity and were first described 16 years ago. Still, little is known about the biology of this aggressive lymphoma. Identical arrays covering 1176 genes (Clontech Human Cancer 1.2) were hybridized with labeled first-strand cDNA from five ALCL cell lines and stimulated T cells. We found overlapping gene expression patterns in the five cell lines. Three genes, tissue inhibitor of metalloproteinases 1 (TIMP-1), nm23-H4, and interferon-induced 56K protein (IFI-56K) were strongly overexpressed in all ALCL cell lines compared with stimulated T cells. Whereas interleukin-2 precursor, interleukin-9 precursor, interferon-gamma precursor, T cell surface glycoprotein CD3 epsilon subunit, 40S ribosomal protein SA, and protein-tyrosine phosphate 1C were underexpressed, Reverse transcription polymerase chain reaction and Northern blot analysis were employed to confirm the expression patterns of the genes identified by Atlas hybridization.