Background: Extramammary Pagets disease (EMPD) is a rare malignant neoplasm of apocrine gland bearing skin characterized by intraepidermal proliferation of adenocarcinoma cells.Tumor growth depends on the ability of tumor cells to migrate by proteolysis and on angiogenesis.The matrix metalloproteinase (MMP) enzymes have been implicated in both of these processes in other types of skin cancer.Methods: The expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, and MMP-19 was analyzed by immunohistochemistry and/or in situ hybridization in 27 EMPD and five mammary PD (MMPD) specimens.The distribution of laminin-5 (LN-5) and tenascin-C, two extracellularmatrix proteins associated with tumor invasion, was studied by immunohistochemistry.Results: MMP-7 (matrilysin-1) and MMP-19 were the most frequently expressed MMPs in Pagets cells.Overexpression of MMP-2, MMP-9, or MMP-13, which is seen in many cancers, was not evident in EMPD.LN-5 and tenascin-C positivity did not correlate with the level of invasion.MMP-7, MMP-13, and MMP-19 were detected abundantly in MMPD, while MMP-9 was absent.Conclusions: MMP expression did not generally associate with the level of invasion of EMPD.In three samples positive for MMP-7 and four samples positive for MMP-19, an underlying carcinoma was detected, suggesting the importance of these two MMPs as predictors of secondary EMPD or the putative origin of Pagets cells from the dermal adenocarcinoma cells of apocrine duct origin. Background: Extramammary Paget’s disease (EMPD) is a rare malignant neoplasm of apocrine gland bearing skin characterized by intraepidermal proliferation of adenocarcinoma cells. Tumor growth depends on the ability of tumor cells to migrate by proteolysis and on angiogenesis. The matrix metalloproteinase (MMP ) enzymes have been implicated in both of these processes in other types of skin cancer. Methods: The expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP- 9, MMP- 13, and MMP- 19 was analyzed by immunohistochemistry and / or in situ hybridization in 27 EMPD and five mammary PD (MMPD) specimens. The distribution of laminin-5 (LN-5) and tenascin-C, two extracellular matrix proteins associated with tumor invasion, was studied by immunohistochemistry . Results: MMP-7 (matrilysin-1) and MMP-19 were the most frequently expressed MMPs in Paget’s cells. Overexpression of MMP-2, MMP-9, or MMP-13, which is seen in many cancers, was not evident in EMPD.LN-5 and tenascin-C positivity did not correlate with t he level of invasion. MMP-9 was absent. Conclusions: MMP expression did not generally associate with the level of invasion of EMPD. In three samples positive for MMP-7 and four samples positive for MMP-19, suggesting the importance of these two MMPs as predictors of secondary EMPD or the putative origin of Paget’s cells from the dermal adenocarcinoma cells of apocrine duct origin.