Node-positive breast carcinoma is an aggressive disease. Postmenopausal patients benefit from antiestrogen adjuvant therapy. Predictive markers could, however, be useful in selecting these patients for different modalities of adjuvant therapy. Recently, we showed that MMP-2 (72 kD type IV collagenase/gelatinase A) is correlated with unfavorable prognosis in premenopausal breast carcinoma patients. Expression of the immunoreactive protein for MMP-2 was evaluated prospectively in this study in paraffin tissue sections from primary tumors of 100 postmenopausal, node-positive breast carcinoma patients treated with an adjuvant antiestrogen therapy. A specific MMP-2 monoclonal antibody in an avidin-biotin immunohistochemical staining was used. Sixty nine percent of the samples were MMP-2 positive. Eighty three percent of the MMP-2 negative patients lived for 5 years without a recurrence, while only 67% of the patients with an MMP-2 positive primary tumor were recurrence-free at that time (p < 0.05; log rank analysis). MMP-2 positivity showed a significant correlation with shortened survival in patients with a small primary tumor (T1-2) and a low axillary tumor burden. One hundred percent of these patients with an MMP-2 negative breast carcinoma survived for 5 years, compared to 73% of the MMP-2 positive cases alive at that time (p = 0.02). In conclusion, we show here that MMP-2 is a prognostic indicator in postmenopausal patients with node-positive breast carcinoma with a low tumor burden, and that it predicts a risk for failure in antiestrogen adjuvant therapy. It might have predictive value in selecting the most efficient adjuvant therapy in this set of patients.