Expression of the p21 product of the ras gene family was investigated in a series of 142 infiltrating primary breast tumors by two specific ras p21 monoclonal antibodies with an immunocytochemical technique. The majority of tumors demonstrated a varying number of positive cells. A significant association between p21 expression and tumor histotype was found: among ductal carcinomas the comedo variety was always positive; conversely, lobular tumors were more frequently negative. Nodal status was recorded for all patients. A significant difference was found in nodal status with respect to p21 expression: tumors with more than 50% positive cells were more often N+. Estrogen receptor (ER) status was determined in 77 tumors. Tumors with higher levels of p21 contained a high percentage of estrogen receptor positive cells. The present results show that p21 expression in human breast cancer could be a marker of tumor aggressiveness and might thus improve the predictive power of known prognostic factors such as estrogen receptor and nodal status.