Based on the prognostic role of Her-2 amplification and protein overexpression in breast cancer, various studies have been performed in oral squamous cell carcinomas (OSCC) with inconsistent results. As in invasive breast carcinomas Her-2 overexpression has been related to an increased number of chromosome 17 copies, a common chromosomal alteration in OSCC, we evaluated the association between polysomy 17 and Her-2 protein expression in a series of primary OSCC. Forty-one incisional biopsies of primary OSCC were included in the study. Protein expression was evaluated immunochistochemically with CB11 mouse monoclonal anti-human antibody. The reaction was arbitrarily characterized as absent, faint, moderate, and strong, and staining pattern as cytoplasmic and membranous. Positive cases were analyzed by chromogenic in situ hybridisation (CISH) to access Her-2 status. The association between polysomy 17 and Her-2 expression was checked by Fisher's exact test. Four cases were negative and 37 cases were positive for Her-2. Staining was faint in 15 cases and moderate in 22 cases. CISH showed that all cases with faint staining were diploid, while from the cases with moderate staining 10 were diploid and 12 polysomic for chromosome 17. Thirteen cases showed purely cytoplasmic staining, while in 24 there were areas of both cytoplasmic and membranous staining. There was a statistically significant correlation between intensity of the reaction and polysomy 17 (P = 0.0036), in particular for cases with both cytoplasmic and membranous staining (P = 0.0128). In some OSCC Her-2 immunohistochemical expression may be associated with chromosome 17 polysomy and not Her-2 amplification.