Gene expression profiles were studied in 13 cases of salivary gland carcinoma including mucoepidermoid carcinoma (MEC), acinic cell carcinoma (ACC), and salivary duct carcinoma (SDC) using a cDNA array. A total of 162 genes were deregulated. Only 5 genes were overexpressed in all carcinomas including fibronectin 1 (FN1), tissue metalloproteinase inhibitor 1 (TIMP1), biglycan (BGN), tenascin-C (HXB), and insulin-like growth factor binding protein 5 (IGFBP5), whereas 16 genes were underexpressed. The small number of similarly deregulated genes in these carcinoma entities suggests an extensive genetic variation between them. This result agrees with the great histopathological diversity of different entities of salivary gland carcinoma. Furthermore, diversity in gene expression between the carcinoma types was identified also by hierarchical clustering. Each carcinoma entity was clustered together but MEC, SDC, and ACC were separated from each other. Significance analysis of microarrays identified 27 genes expressed differently between the groups. In MEC, overexpressed genes included those of cell proliferation (IL-6 and SFN) and cell adhesion (SEMA3F and COL6A3), whereas many underexpressed genes were related to DNA modification (NTHL1 and RBBP4). Apoptosis-related genes CASP10 and MMP11 were overexpressed in SDC, in accordance with the typical tumor necrosis seen in this entity. An intermediate filament protein of basal epithelial cells, cytokeratin 14 (KRT14) was clearly differently expressed between the 3 types of carcinoma, and can be used as an aid in their differential diagnosis. The array results were validated by RT-PCR and immunohistochemistry.