Background: Protrusive structures formed by migrating and invading cells are termed lamellipodia, filopodia,invadopodia and podosomes. Lamellipodia and filopodia appear on the leading edges of migrating cells andfunction to command the direction of the migrating cells. Invadopodia and podosomes are special F-actin-richmatrix-degrading structures that arise on the ventral surface of the cell membrane. Invadopodia are found in avariety of carcinomatous cells including squamous cell carcinoma of head and neck region whereas podosomesare found in normal highly motile cells of mesenchymal and myelomonocytic lineage. Invadopodia-associatedprotein markers consisted of 129 proteins belonging to different functional classes including WASP, NWASP,cortactin, Src kinase, Arp 2/3 complex, MT1-MMP and F-actin. To date, our current understanding on therole(s) of these regulators of actin dynamics in tumors of the orofacial region indicates that upregulation ofthese proteins promotes invasion and metastasis in oral squamous cell carcinoma, is associated with poor/worstprognostic outcome in laryngeal cancers, contributes to the persistent growth and metastasis characteristicsof salivary gland adenoid cystic carcinoma, is a significant predictor of increased cancer risk in oral mucosalpremalignant lesions and enhances local invasiveness in jawbone ameloblastomas.