The aim of this study was to evaluate the influence of laminin-5 (LN-5) gamma2 chain immunohistochemistry on the assessment of invasiveness in cervical adenocarcinomas and its impact on the diagnostic reproducibility of glandular lesions of the cervix uteri. Immunohistochemistry with LN-5 gamma2 was performed on 30 cases, including 12 adenocarcinomas in situ (AISs), 5 AISs that were suggestive, albeit not conclusive, of infiltration (AIS+), 7 frankly invasive adenocarcinomas, and 6 nonneoplastic cases with reactive changes. Diagnostic agreement between 3 observers was evaluated by kappa statistics in routine histologic specimens and with the aid of LN-5 gamma2 immunohistochemistry. Laminin-5 gamma2 was expressed in 5 of the 12 AISs (41.6%), all AIS+ and invasive adenocarcinomas, and none of the reactive cases. Cytoplasmatic staining was detected at the invasion front of frankly invasive adenocarcinomas and in tumor buds of all AISs with minimal stromal infiltration. Overall, interobserver agreement was significantly improved by adding LN-5 gamma2 immunostains to the conventional slides (0.56 versus 0.86; P = .002). The difference in interobserver agreement further increased when including only AISs and AIS+ in the analysis (0.17 versus 0.72; P = .000). After immunohistochemical evaluation, the original AIS diagnosis was unanimously changed to adenocarcinoma with minimal stromal invasion in 3 of 12 cases (25%), whereas a discordant hematoxylin-eosin diagnosis turned into a concordant one in 10 of 13 cases (6 AISs, 2 AIS+, 2 adenocarcinomas; 76.9%). Immunohistochemistry with LN-5 gamma2 facilitates the assessment of the invasiveness of cervical adenocarcinomas and improves the interobserver agreement in glandular lesions of the cervix uteri.