The clinicopathologic features in a series of 21 chromophobe cell carcinomas are reviewed. Patients' ages ranged from 30 to 83 years (mean, 53 years), and the number of men and women was roughly equal. Major presenting complaints included hematuria, flank pain, and flank mass. All but two tumors were staged as tumor node metastasis (TNM) T2N0M0. Histologically, the carcinomas were composed of large cells with variably reticulated, translucent cytoplasm. The tumor cells could be divided into three types according to the extent and distribution of reticulated cytoplasm. Ultrastructurally, these reticulated areas were characterized by the presence of large numbers of microvesicles, which appeared to be unique to chromophobe cell carcinomas because ultrastructural examination of 20 clear cell carcinomas and six granular cell carcinomas failed to reveal similar structures. The origin of the vesicles appeared to be from saccular outpouchings from the outer mitochondrial membrane. Immunohistochemical studies revealed that all the tumors were variably positive for cytokeratins 8, 18, and 19, and epithelial membrane antigen but negative for vimentin. Flow cytometric DNA analysis of eight carcinomas revealed slightly hypodiploid cell populations in seven tumors. Of these, four also contained hyperdiploid cell populations. Follow-up (6-108 months) of 16 patients revealed all these patients to be alive and well. These findings further confirm the concept that chromophobe cell carcinoma is a special subtype of renal cell carcinoma in which the presence of microvesicles is a characteristic morphologic feature. Furthermore, loss of chromosomal DNA may also be a frequent, perhaps unique, feature of chromophobe cell carcinoma.