Among the benign epithelial odontogenic tumors, the ameloblastoma occupies a special place because of their local aggressive behavior with devastating jaw destructions, which lead to a high recurrence rate, even following the radical surgery. In an attempt to clarify the mechanisms underlying this behavior we immunohistochemically investigated the reactivity of different histological variant of ameloblastoma to MMP-9, TIMP-2, E-cadherin and vimentin. A semiquantitative assessment of their reactivity in the epithelial neoplastic compartment was done and statistical correlation was attempt with histological variant and between them. The MMP-9 and TIMP-2 reactivity was observed with variable intensity both in the neoplastic epithelium and in the stroma that surround the ameloblastic proliferations. Only for MMP-9, the statistical tests proved the existence of significant differences within major ameloblastic histological variants, with the highest reactivity acanthomatous type. The stroma independent of the histological variant had the highest reactivity at the invasive front adjacent to the tumoral islands. Immunoreactivity for E-cadherin was more obvious in the follicular type at the level of stellate-reticulum like cells, and decreased in the peripheral columnar cells, as they are closer to the invasion front. Vimentin reactivity was present in the neoplastic epithelium only in the peripheral columnar cells at the invasion front but at this site, the stroma had the highest expression. Statistical analysis proved the existence of inverse relationship between MMP-9 and E-cadherin scores, while vimentin score had an inverse relationship both with TIMP-2 and E-cadherin scores. Our results proved the implication of these four markers in the growth of ameloblastomas and as a consequence their utility in monitoring of local aggressiveness of these tumors.