Abstract: Objective To analyze the clinical and histopathological features of 100 cases of scrotal Paget′s disease. Methods Specimens were collected from 100 outpatients with scrotal Paget′s disease evaluated in the Department of Dermatology, Huashan Hospital, Fudan University during the period of 1987-2004. Clincal data as well as findings in the examination with H&E staining, special staining and immunohistochemical staining were retrospectively assessed for these cases. Results Three types of tumor cells were observed in these specimens, including typical Paget cells （51 cases）, mucinous or signet-ring cells （11 cases）, small cells （18 cases）. Mixed types of tumor cells were seen in 20 cases. Paget cells spread in the epidermis in three patterns （sparsely, intensively and classically）. Tumor cells could extend down along the epithelium of follicles or sweat glands, ultimately broke through dermal-epidermal junction or the basal membrane of adnexa, and migrated into the dermis. Conclusions Histopathological examination is the most important clue to the diagnosis of scrotal Paget′s disease. Histologically, it should be differentiated from superficial spreading malignant melanoma, skin lymphoma, pagetoid squamous cell carcinoma in situ and secondary scrotal Paget′s disease.