A set of best practices for the conduct of histopathology evaluation in nonclinical safety studies was endorsed by the Society of Toxicologic Pathology (STP) in 2004. These best practices indicate that the study pathologist should have knowledge of the treatment group and access to all available study-related data for the animal from which the tissue was obtained. A new set of best practices for the conduct of histopathology review for safety biomarker qualification for nonclinical studies has been endorsed by the STP and is summarized in this document. These best practices are generally similar to those for nonclinical safety studies, specifically that the pathologist be “unblinded” or have access to study data. Although histopathology evaluation in biomarker qualification studies must be performed without knowledge of novel biomarker data, the study pathologist(s) should be involved in the attendant meta-analyses of these data. Blinded evaluation is an experimental tool in biomarker qualification studies that is appropriate only when well-defined criteria for specific histopathologic findings are identified prior to blinded review. Additionally, this paper also considers the management of bias, the use of a tiered evaluation approach, the importance of using qualified pathologists and standard reporting, and the management of spontaneous findings.