Polymorphous low-grade adenocarcinoma (PLGA) and adenoid cystic carcinoma (ACC) have several overlapping histological patterns, including cribriform, tubular and solid patterns. The overlapping clinicopathological features of PLGA and ACC may result in a diagnostic pitfall. ACC has a much worse prognosis than PLGA, making differentiation important for therapeutic and prognostic purposes. Histopathological features remain the most reliable criteria to distinguish between these two tumours. Although PLGA and ACC have many features in common, PLGA is uncommon in the major salivary glands. Histopathological distinction is therefore mainly a problem in tumours of minor salivary gland origin where small biopsies often contribute to diagnostic difficulties. This paper reviews studies which have utilised several immunohistochemical markers in attempts to distinguish between PLGA and ACC, and also studies which have focussed on the two tumours individually. The potential discriminating value of immunohistochemistry between cases of PLGA and ACC still remains controversial.