OBJECTIVE: Our purpose was to examine the relationship between HER- 2/neu expression and human papillomavirus infection in cervical glandular neoplasia. STUDY DESIGN: Cases of cervical adenocarcinoma in situ and invasive adenocarcinoma were selected for study. Human papillomavirus typing was performed by in situ hybridization. HER-2/neu was detected by in situ hybridization and immunohistochemistry. Fisher's exact test was used to assess for statistical significance. RESULTS: Fifteen cases of adenocarcinoma in situ and invasive adenocarcinoma were analyzed. In situ hybridization detected HER-2/neu messenger ribonucleic acid in 8 cases, whereas immunohistochemistry detected protein in 5 cases. Overall, HER-2/neu activity was present in 10 cases (66.7%). HER-2/neu messenger ribonucleic acid was detected more commonly in lesions associated with human papillomavirus type 16 versus type 18 (85.7% vs 25.0%, p = 0.04). CONCLUSION: HER-2/neu is frequently expressed in human papillomavirus-infected glandular lesions of the cervix. In situ hybridization may provide a more sensitive indicator of HER-2/neu activity over immunohistochemistry. Preferential expression of HER- 2/neu messenger ribonucleic acid was detected in human papillomavirus type 16 versus type 16 lesions. Further study is warranted to examine relationships between human papillomavirus infection and HER-2/neu expression.