The differential diagnosis of acinic cell carcinoma with high-grade transformation includes high-grade neoplasms of salivary and non-salivary origin. These entities include: 1) Adenoid cystic carcinoma with high-grade transformation - they usually have foci with typical morphology showing cribriform-tubular growth pattern. There is dual cell population of p63-negative ductal cells and p63-positive outer basal/myoepithelial cells. 2) Basal cell adenocarcinoma - show peripheral palisading and a population of p63-positive tumor cells. 3) Metastases from occult breast or prostate primary - a panel of breast or prostate immunohistochemical markers can help arrive at the correct diagnosis. 4) Salivary duct carcinoma - these tumors show apocrine differentiation and have eosinophilic rather than basophilic cytoplasm and are androgen receptor-positive. 5) Squamous cell carcinoma - they will usually show obvious signs of squamous differentiation such as keratinization or squamous pearls and are p63 positive.