Five cases of extramammary Paget's disease of the vulva were studied by histologic, ultrastructural, and immunologic methods. In one of these cases, the associated invasive adnexal carcinoma was studied in a similar fashion. In all five cases, carcinoma-in situ of the sweat glands was observed. In two cases, the glands were identified as aporcrine. In the other three it could not be determined whether they were apocrine or eccrine. In one case tumor cells were seen extending from a focus of underlying carcinoma-in-situ of sweat glands through the excretory duct into the surface epithelium. The ultrastructural findings indicated that the Paget's cells as well as the cells of the invasive carcinoma were adenocarcinoma cells, but the findings were not conclusive as to whether the cells were apocrine or eccrine. There was no evidence of origin of the Paget's cells from keratinocytes. We believe that the bulk of evidence favors an extraepidermal origin for extramammary Paget's disease. The tumor is most commonly derived from the secretory portion of sweat glands, probably either of apocrine or eccrine types, or the dermal or poral portion of the sweat duct. Some cases of Paget's disease are derived from other types of glands.