Nevoid basal cell carcinoma syndrome (NBCCS), an autosomal dominant disorder, is characterized by the development of numerous cutaneous basal cell carcinomas (BCCs). To better characterize this disorder, we examined the expression of matrix metalloproteinase-3 (MMP-3; also known as stromelysin-1) in BCC tumor specimens, adjacent normal skin, and fibroblasts isolated from the normal-appearing skin of NBCCS patients. Three of three BCC tumors obtained from NBCCS patients overexpressed MMP-3 mRNA. In contrast, only 25% of BCC specimens in patients without NBCCS demonstrated overexpression of MMP-3 mRNA. Moreover, fibroblasts isolated and cultured from all nine uninvolved skin specimens of NBCCS patients overexpressed MMP-3 mRNA. MMP-3 mRNA was not detected or was detected at very low levels in normal skin and fibroblast cultures isolated from normal skin in nonsyndrome patients.