Stromelysin-3 is produced in the stroma of various malignant tumors, and in breast carcinoma there seems to be a positive correlation between aggressive disease and intensity of stromelysin-3 expression, suggesting that stromelysin-3 participates in the tumor spread. In basal cell carcinoma, previous findings on stromelysin-3 have been inconclusive in this respect. Our study was undertaken to determine the pattern of stromelysin-3 production in relation to different histologic subtypes and stromal reactions in basal cell carcinoma. By in situ hybridization, stromelysin-3 mRNA was detected in stromal fibroblastic cells in 51/56 samples. Furthermore, there was a significant correlation between strong signal for stromelysin-3 mRNA and infiltrative tumor growth. In all tumors, there was ongoing collagen synthesis as shown by a signal for procollagen I mRNA; this signal co-localized with stromelysin-3 around tumor nests. Our findings suggest a link between stromelysin-3 and fibrotic stromal response, which prompted us to evaluate the expression of stromelysin-3 in other fibrotic skin tumors. Interestingly, stromelysin-3, co-localizing with procollagen I mRNA, was consistently expressed in lesional cells in dermatofibromas (19/19), but not in dermatofibrosarcomas (0/7). Thus, our results indicate that in addition to being a marker for malignant disease, stromelysin-3 is produced by fibroblastic cells associated with benign fibrosis. A subset of cells producing stromelysin-3 appears to be myofibroblasts as demonstrated by immunoreactivity for alpha smooth muscle actin in both basal cell carcinoma and dermatofibroma.