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This study aimed to develop and validate an artificial intelligence-based cancer cell detection model for detecting breast carcinoma in bright-field in situ hybridization (ISH) whole-slide images, with the goal of improving cancer cell selection prior to the quantification of HER2 and CEP17 gene copies. The difference in IA performance was not statistically significant compared to visual assessment in quantifying the HER2\/CEP17 ratio and average HER2 copy numbers per cell. However, IA with the Cancer Cell Detection Module (IA 2.0) quantified consistently higher values than IA without (IA 1.0). Cancer cell detection in IA 1.0 showed 64% sensitivity, 83% specificity, and a positive predictive value (PPV) above 95% for samples with at least 84% cancer cellularity. IA 2.0 improved cancer cell detection sensitivity to 69% and specificity to 93%, achieving a PPV above 95% for samples with at least 66% cancer cellularity. IA 2.0 showed 95% concordance with visual scoring (\n                    <jats:italic>k<\/jats:italic>\n                    \u2009=\u20090.90), with 90% sensitivity and 100% specificity. Discordant cases required the selection of a second cancer cell-enriched region of interest, shifting classification from HER2-negative to HER2-positive. After correction, IA 2.0 achieved full agreement with visual classification (100%,\n                    <jats:italic>k<\/jats:italic>\n                    \u2009=\u20091.000), underscoring the critical role of the pathologist supervision in this assay.\n                  <\/jats:p>","DOI":"10.1007\/s00428-026-04534-x","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T03:44:27Z","timestamp":1777002267000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Artificial intelligence enhances cancer cell selection for HER2 gene amplification assessment in breast carcinoma"],"prefix":"10.1007","author":[{"given":"Iv\u00e1n","family":"Rienda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catarina","family":"Eloy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8312-1681","authenticated-orcid":false,"given":"Ant\u00f3nio","family":"Pol\u00f3nia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"issue":"1","key":"4534_CR1","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1186\/s12885-025-13862-1","volume":"25","author":"M Elmadani","year":"2025","unstructured":"Elmadani M, Mokaya PO, Omer AAA, Kiptulon EK, Klara S, Orsolya M (2025) Cancer burden in Europe: a systematic analysis of the GLOBOCAN database (2022). 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Ethical approval and informed consent were not required for this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"CE consulted in the last 2\u00a0years for Diapath, Sakura, Biocartis, Page AI and Epredia. AP consults for Indica Labs. The authors declare no other potential conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}