Anaplastic large cell lymphomas (ALCL) are characterised by the presence of CD30-positive large cells, which usually are of T-cell type. Based on the presence or absence of translocations involving the anaplastic lymphoma kinase (ALK) locus, ALCL cases can be divided into two groups. To gain more insight in the biology of ALCL, we applied serial analysis of gene expression (SAGE) on the Karpas299 cell line and identified 25 up- and 19 downregulated genes. Comparison of the differentially expressed genes with DNA copy number changes in Karpas299 revealed that two overexpressed genes, S100A10 and S100A11, were located in an amplicon suggesting that the increased mRNA levels were caused by DNA amplification. Quantitative reverse transcription polymerase chain reaction on 5 ALCL cell lines and 12 ALCL tissues confirmed the SAGE data for 13 out of 14 up- and one out of four downregulated genes. Immunohistochemical staining confirmed the presence of S100A10, a calcium-binding protein, in three out of five ALK+ and all 7 ALK- ALCL cases. S100A11 staining was confirmed in all ALK+ and six of seven ALK- ALCL cases. Three of the upregulated genes represented calcium-binding proteins, which suggest that altered intracellular signaling might be associated with the oncogenesis of ALCL.