mRNA expression of stromelysin-3 (ST3) and 72K type IV collagenase (cIVase) in 4 human breast cancer cell lines and 55 resected breast tumors were examined using Northern blot analysis. In 4 cell lines ST3 was not expressed at all, while cIVase gene expression was detected in 3 of them. The ST3 expression was found more specifically in malignant tumors (39/40, 97.5%) than in benign ones (4/15, 26.7%), although cIVase was expressed in all tumor specimens. The quantitative analysis showed that ST3 expression in malignancies was significantly greater than that in benign tumors (P = 0.0007), while cIVase expression was not (P = 0.1381). ST3 gene expression was also closely related to the presence of lymph node metastasis (P = 0.047), while cIVase was not (P = 0.1091). These results suggest, therefore, that ST3 is expressed more specifically by stromal cells surrounding cancer cells than cIVase. Since ST3 mRNA expression was independent of the EGFR, ER and erbB2 protein expression, ST3 may be a new potent prognostic guide for breast carcinomas, which can detect highly malignant subpopulations.