Adenoid cystic carcinoma (ACC) of salivary gland is one of the most common epithelial salivary gland carcinomas and is characterized by extensive local tissue infiltration and poor long-term survival. All forms of ACC are characterized by prolonged but persistent growth, extensive perineural invasion and hematogenous metastases. Distant sites of metastasis are primarily lung, although bone and liver are also common. The incremental motility of malignant cells is a critical step in their migration, invasion and metastasis, which is regulated by reorganization of actin cytoskeleton and regulation of focal adhesion. Fascin-1 and ezrin are essential components of these cellular structures. The aim of this study is to evaluate the expression of these cytoskeleton-associated proteins in ACC as a prognostic indicator of invasiveness. Five cases of normal salivary gland tissue and 43 cases of adenoid cystic carcinoma (10 cases cribriform form, 15 cases tubular form and 18 cases solid form). Immunohistochmical staining for ezrin and fascin-1 antibodies were done for all specimens. Statistical analysis was performed using a commercially available software program (SPSS 19; SPSS, Chicago, IL, USA). The level of significance was set at P < 0.05. For both markers, statistically, the greatest mean area percent was recorded in solid pattern ACC, whereas the lowest values were recorded in normal tissue. These results indicating a synergistic effect between ezrin and fascin-1 during ACC invasion.