The expression of vimentin, alpha-smooth muscle actin (alpha-SMA) and c-kit in adenoid cystic carcinomas (AdCCs) and polymorphous low-grade adenocarcinomas (PLGAs) was investigated immunohistochemically to evaluate the application of these markers to distinguish AdCCs from PLGAs when the histological features are equivocal. Tissue specimens of AdCCs and of PLGAs, formalin-fixed and paraffin-embedded were retrospectively studied using vimentin, alpha-SMA and c-kit. Positive staining for alpha-SMA was identified in all AdCCs and 25% of PLGAs. The immunoreactivity of c-kit in all positive cases of AdCCs (83%) and PLGAs (41%) was more than 50% and less than 50% of tumor cells respectively. The expression pattern for both alpha-SMA and c-kit, in tubular structures of AdCCs was different of that seen in the same structures in PLGAs. The results of this study support the potential application of alpha-SMA and c-kit as an adjunctive aid in the differential diagnosis of AdCCs from PLGAs.