In a subset of cases, metastatic renal cell carcinoma can demonstrate significant morphologic overlap with germ cell neoplasms, making accurate diagnosis challenging. In such cases, immunohistochemistry is often used as an adjunct diagnostic tool. Expression of the putative renal cell carcinoma markers PAX-2, PAX-8, and hKIM-1 has been reported in a small series of certain germ cell tumors, raising doubt about their specificity for renal cell carcinoma. To further characterize these markers, we evaluated PAX-2, PAX-8, and hKIM-1 staining in 100 germ cell tumors using tissue microarrays. PAX-2 and PAX-8 staining was identified in 50% and 25% of yolk sac tumors (respectively), with hKIM-1 staining identified in 48% of embryonal carcinomas and 50% of yolk sac tumors. All other germ tumor cells (notably including 62 seminomas) were negative for all 3 markers, in contrast to prior reports of PAX-8 reactivity in seminoma. This study indicates that PAX-2, PAX-8, and hKIM-1 should be used cautiously in distinguishing renal cell carcinoma from nonseminomatous germ cell neoplasia and also adds to the growing list of nonrenal tumors that express these 3 markers.