Tumors derived from choroid plexus epithelium are uncommon and may exhibit a wide variety of histologic patterns. They often are difficult to distinguish from metastatic carcinomas. Previous studies that addressed this issue yielded conflicting results. Recent reports have demonstrated that evaluation of coordinate expression of cytokeratin (CK) 7 and CK20 aids in distinguishing primary from metastatic lesions in a number of anatomic sites and that tumors that commonly are metastatic to the brain retain their CK7/CK20 immunophenotype in this location. We examined 35 choroid plexus tumors with a panel of antibodies to determine their CK7/CK20 immunophenotype. Tumors from 35 patients (7 male, 28 female; mean age, 25 years), including 31 choroid plexus papillomas and 4 atypical papillomas, were evaluated. All tumors were intraventricular or within the cerebellopontine angle and composed predominantly of orderly columnar epithelial cells resting on distinct fibrovascular cores. Atypical papillomas contained combinations of focal loss of architectural pattern, increased mitotic activity, necrosis, and brain parenchymal invasion. No lesion was unequivocally malignant. Twenty-six tumors (74%), including all atypical papillomas, were CK7 positive and CK20 negative. Two tumors stained with both markers, one stained with CK20 only, and six stained with neither marker. Other findings included expression of glial fibrillary acidic protein in 24 tumors, S-100 protein in 19 tumors, transthyretin in 31 tumors, Ber EP4 in 1 tumor, CAM5.2 in 33 tumors, epithelial membrane antigen in 4 tumors, and pancytokeratin in 27 tumors. Our results indicate that the majority of choroid plexus tumors have a CK7-positive/CK20-negative immunophenotype. This finding may be useful in differentiating these lesions from metastatic carcinomas that have differing CK7/CK20 profiles.