BACKGROUND:Although largely readily recognizable in tissue sections, acinic cell carcinoma (ACC) remains diagnostically problematic in fine-needle aspiration (FNA) cytopathology. The authors undertook an analysis of a large series of ACC aspirates, including acinic cell carcinoma with high-grade transformation (ACC-HGT). METHODS: The authors searched their cytopathology files for ACC cases with histopathologic confirmation. FNA biopsy was performed according to standard techniques. RESULTS: Fifty FNA biopsy cases of ACC (including 36 of parotid origin [72%]) from 41 patients (female to male ratio, 1.4:1; age range, 23-84 years; average, 54 years) met the study inclusion requirements. Primary neoplasm aspirates were most common (72%), and they were followed by recurrent tumors (16%) and metastases (12%). A precise cytologic diagnosis was made for 64%. Three of 9 ACC-HGT cases (33%) were correctly interpreted as such; 98% of conventional ACC cases were correctly graded as low-grade. With the Milan classification system, 74% fit into the malignant category.Ancillary testing was performed for only 36%. Conventional ACC had moderately to highly cellular smears; monotonous cells in aggregates and single forms; rounded nuclei; and microvacuolated, finely granular, oncocyte-like, or nonspecific cytoplasm. ACC-HGT smears contained larger nuclei, high nuclear to cytoplasmic ratios, coarse nuclear chromatin, and a loss of cytoplasmic granules/vacuoles. CONCLUSIONS: A correct diagnosis of ACC via FNA biopsy was made in almost two-thirds of the cases. With the Milan classification, 84% of the cases would have been classified as malignant or suspicious for malignancy. An absence of conventional serous acinar cell morphology in some cases as well as an absence of ancillary immunohistochemistry testing in almost two-thirds of the cases prevented even better diagnostic performance. Cancer