Abstract. SMAD4, also known as DPC4 (deleted in pancreatic carcinoma 4) was initially identified as a tumor-suppressor gene. It is located on 18q21, a region frequently deleted in pancreatic carcinoma. Functionally inactivating mutation of the gene also occurs in many cases of pancreatic cancer. Functional loss of SMAD4 is frequently detected not only in pancreatic carcinoma but also in colorectal carcinoma. However, in other human cancers, SMAD4 aberrations are seen only occasionally. The purpose of this study was to elucidate the role of SMAD4 in adenoid cystic carcinoma of the salivary glands. We examined 34 cases of adenoid cystic carcinoma for loss of heterozygosity (LOH) of the SMAD4 locus and for the existence of mutations of the gene. LOH was detected in 2/14 informative cases. No mutations were detected in any of the 34 cases. In conclusion, the infrequent LOH of the SMAD4 gene locus and lack of SMAD4 mutations indicate that SMAD4 does not play a role in the tumorigenesis of adenoid cystic carcinoma of the salivary gland.