Proto-oncogenes represent a family of normal cellular genes that were identified on the basis of their similarity to genetic sequences with known tumorigenic or transforming potential. Accumulating evidence links alterations in either the structure, copy number, or expression of one or another of these genes to neoplasia. One such gene, called erbB-2/Her-2 was found amplified in an adenocarcinoma of the human salivary gland and has also been found associated with primary human breast cancer. Patients with multiple copies of the gene have had a shorter overall survival. In the present study, 21 tumors of the parotid gland were examined by Southern and Northern blot hybridization for amplification and possible overexpression of the erbB-2/Her-2 oncogene. Normal parotid gland tissue was used as negative control. The parotid gland lesions comprised 7 pleomorphic adenomas, 5 squamous cell carcinomas, 4 cases of chronic fibrotic sialadenosis, 3 mucoepidermoid carcinomas as well as 1 lymphoma and 1 cystadenolymphoma. Gene amplification was found in 1 of the pleomorphic adenomas, with 2 tumors showing a significant overexpression of the erbB-2/Her-2 oncogene. Because 3-5% of all pleomorphic adenomas undergo malignant transformation, close follow-up of patients is currently underway.