To evaluate the relationship between the c-kit proto-oncogene product and malignant transformation of human breast tissue, we examined the immunohistochemical expression of the c-kit proto-oncogene product in both malignant and non-malignant breast tissues. The immunohistochemical expression of the c-kit proto-oncogene product in 40 primary breast cancer tissues (22 axillary lymph nodes negative, 18 lymph nodes positive), in 18 corresponding axillary lymph nodes, and in 10 distant metastastic tissues were studied using an anti-c-kit proto-oncogene product antibody in comparison with 20 normal and 20 benign breast tissues. The mean values of immunoreactive score (IRS) were compared. The IRS of the c-kit proto-oncogene product in normal mammary epithelia was 5.90 +/- 1.37 (mean +/- s.d.). In benign tissues, the c-kit proto-oncogene product was detected heterogeneously with a reduced IRS (4.05 +/- 1.82). In primary breast cancer tissues, the expression of the c-kit proto-oncogene product was often deleted and the average IRS (0.90 +/- 1.73) was significantly reduced compared to those of the normal breast tissues or benign breast disease tissues, but no significant difference was shown between the breast cancer groups. The c-kit proto-oncogene product may correlate with growth control or the differentiation of normal breast epithelium. This result suggests that the loss of expression of this protein might correlate with malignant breast cancer progression, but it is most likely involved at an early stage of human breast cancer development.