SummaryThe histogenesis of mammary Paget's disease (MPD) and extramammary Paget's disease (EMPD) cells remains controversial. The purpose of this study was to investigate MPD and EMPD immunohistochemically with antibodies to some tumour markers (Ca 15‐3, KA‐93 and Ca 19‐9), and a cell surface receptor for hyaluronate (CD44), as these have been shown to be expressed in normal eccrine or apocrine glands and/or the epidermis, as well as some tumours. Surgically excised, formalin‐fixed, paraffin‐embedded tissues, or frozen tissues, from seven mammary, five vulvar, two scrolal and two axillary lesions were studied.Paget cells stained strongly with antibodies to Ca 15‐3 and KA‐93, but did not stain with those to Ca 19‐9 and CD44. Staining with the antibody to Ca 15‐3 was also observed in the ductal and secretory portions of the eccrine and apocrine glands, and in the sebaceous gland cells. Staining with the antibody to KA‐93 was also seen in the apocrine secretory coils, lactiferous duct, epidermal dendritic cells, and cells in the dermal inflammatory infiltrate. Staining with the antibody to Ca 19‐9 was observed only in the eccrine duct, and that to CD44 was seen in eccrine secretory cells and epidermal keratinocytes.These findings suggest that the origin of Paget cells may be the secretory cells of apocrine sweat glands (in EMPD) or the luminal lactiferous ducts (in MPD). We found that the antibodies to Ca 15‐3 and CD44 were useful in differentiating Paget cells from surrounding keratinocytes, by showing positive and negative immunor