Purpose: To examine whether herpes zoster antigen (also called varicella-zoster virus antigen) was detectable in temporal artery biopsies taken from individuals with giant cell arteritis (GCA). Design: Retrospective comparative case series. Methods: Sections of formalin-fixed paraffin-embedded temporal arteries were examined first by hematoxylin-eosin (H&E) staining to establish the diagnosis of GCA. Adjacent sections of the same biopsy were then examined by immunohistochemistry, using 2 different monoclonal antibodies against a major antigen of varicella-zoster virus called gE. Pathologic specimens were obtained from patients cared for at the University of Iowa and Washington University in St. Louis ophthalmology clinics. Results: The study included biopsies from 25 patients with symptoms of GCA as well as positive H&E pathology and 25 patients with symptoms compatible with GCA but negative H&E pathology. Among the GCA-positive group, 3 patients had positive staining for herpes zoster antigen. Among the GCA-negative group, herpes zoster antigen was not detected in any biopsy. In both groups of patients, false-positive staining for herpes zoster antigen was detected in the presence of calcifications in the arteries. False-positive staining was also detected on some extra-arterial skeletal muscle and erythrocytes. Conclusion: Herpes zoster antigen was detected in 3 of 25 temporal arteries from patients with biopsy-proven GCA. One of the 3 positive cases was noteworthy because the patient had had herpes zoster ophthalmicus diagnosed 3 weeks before the onset of GCA symptoms. False-positive staining for herpes zoster antigen was detected on several temporal artery biopsies.