ChatGPT is an artificial intelligence capable of processing and generating human-like language. ChatGPT's role within clinical patient care and medical education has been explored; however, assessment of its potential in supporting histopathological diagnosis is lacking. In this study, we assessed ChatGPT's reliability in addressing pathology-related diagnostic questions across 10 subspecialties, as well as its ability to provide scientific references. We created five clinico-pathological scenarios for each subspecialty, posed to ChatGPT as open-ended or multiple-choice questions. Each question either asked for scientific references or not. Outputs were assessed by six pathologists according to: 1) usefulness in supporting the diagnosis and 2) absolute number of errors. All references were manually verified. We used directed acyclic graphs and structural causal models to determine the effect of each scenario type, field, question modality and pathologist evaluation. Overall, we yielded 894 evaluations. ChatGPT provided useful answers in 62.2% of cases. 32.1% of outputs contained no errors, while the remaining contained at least one error (maximum 18). ChatGPT provided 214 bibliographic references: 70.1% were correct, 12.1% were inaccurate and 17.8% did not correspond to a publication. Scenario variability had the greatest impact on ratings, followed by prompting strategy. Finally, latent knowledge across the fields showed minimal variation. In conclusion, ChatGPT provided useful responses in one-third of cases, but the number of errors and variability highlight that it is not yet adequate for everyday diagnostic practice and should be used with discretion as a support tool. The lack of thoroughness in providing references also suggests caution should be employed even when used as a self-learning tool. It is essential to recognize the irreplaceable role of human experts in synthesizing images, clinical data and experience for the intricate task of histopathological diagnosis.

The authors have declared no competing interest.

This study did not receive any funding.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes