Retrospective review of diagnostic histopathology samples in secondary research projects may generate cases with discordance in diagnosis between the pathologist originally signing out the sample and the reviewer. In this article the authors discuss ethical and legal issues involved in secondary review and propose how diagnostic discrepancies in research projects can be handled. Research participants have the right to know about and control the handling of personal data. Researchers have a duty to inform research participants about research findings of relevance to the current or future health or quality of life. Such feedback is to be provided within a healthcare framework. The authors recommend that pathology laboratories should require researchers to provide feedback on diagnostic discrepancies of potentially clinical significance in secondary research projects using retrospective review of diagnostic histopathology material. The pathology laboratory in charge of the archival material should be responsible for the follow-up on such cases.