This study was planned to evaluate the feasibility of using the assay of leukocyte arylsulfatase-A (AS-A) activity as a non-invasive diagnostic tool in patients with benign and malignant breast disease. The leukocyte AS-A activity of a total of 81 women was analyzed, including 28 healthy women, 29 women with benign breast disease (BBD) and 24 patients with primary breast cancer (BC). The mean leukocyte AS-A activity in patients with BBD was slightly higher (14.3%) that observed in the healthy subjects, but the difference was not statistically significant. In patients with BC the enzyme activity was significantly higher than in the healthy subjects (60.3%, P<0.05) and in the benign group (40.2%, P<0.05). In addition, since no significant differences have been observed between premenopausal patients and their controls, it is suggested that the measurement of leukocyte AS-A activity may not be a reliable test for differential diagnosis of benign and malignant proliferation in mammary glands due to the possible interfering effect of gonadal hormones on AS-A activity. In contrast, since peri- and postmenopausal BC patients have negligible or no gonadal activity function, the elevation in the activity of leukocyte AS-A in these age groups of patients may only be expected to originate from malignant proliferation. Based on our results, it is concluded that in patients in whom high leukocyte AS-A activities were observed the possibility of the presence of malignancy might also be high. Therefore, this test might be valuable as a non-invasive biochemical technique in combination with other established markers for the identification of masses in the breast.