With the use of immunohistochemical techniques, we examined the expression of ras oncogene product p21 in 4 cases of mammary and 13 cases of extramammary Paget's disease. In every mammary case, positive immunostaining was observed in Paget's cells and the underlying tumor (in the 3 cases where a tumor was present). Among the extramammary cases, the cells in 6 cases were immunoreactive. In 4 of these positive extramammary cases, dermal invasion and metastases of regional lymph nodes were observed. Another 2 extramammary cases were weakly reactive. An enhanced expression of ras p21 therefore seems to depend on the region of the tumor or on the biologic behavior. This work suggested that an enhanced expression of ras p21 in Paget's cells may represent a new clinical marker for tumors in cases of mammary and extramammary Paget's disease.