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Background: To analyse outcome with regard to histological features in patients treated for adenoid cystic carcinoma (ACC) in the VU University Medical Center, Amsterdam, The Netherlands. Material–methods: All cases of ACC of the head and neck treated between 1979 and 2009 were analysed through a medical chart review and histopathological revision. Recurrence patterns and possible histological prognostic factors such as histological subtype according to Perzin and Szanto’s grading system (grade I: predominantly tubular, no solid component, grade II: predominantly cribriform, less than 30% solid and grade III: solid component >30%), surgical margins (positive, close and clear) and perineural invasion (PNI) were analysed. Uni- and multivariate statistical tests were performed with SPSS version 15.0® (IBM, New York, USA). Results: One-hundred and five cases of ACC of the head and neck were identified. The most affected major salivary gland was the parotid gland. With regard to the minor salivary glands, the oral cavity and oropharynx were the predominant sites for ACC. Five-, ten- and twenty-year survival rates for disease specific survival (DSS) were 73%, 53% and 45%, respectively. For overall survival (OS) values were 68%, 49% and 25%, respectively. 89% of cases showed positive or close surgical margins, where the group of clear surgical margins mainly consisted of T1–2 major salivary gland tumors. Surgical margins were a significant factor for DSS (p =0.004) as well as for OS (p <0.000). Hazard Ratios (HR) for OS in patients with positive and close surgical margins were 8.1 and 2.3, respectively. With regard to histological subtype, 26% of cases were grade I, 47% grade II and 27% grade III. DSS (p <0.000) and OS (p <0.000) were highly significant. On multivariate analysis, HR for OS was 2.7 for grade II and 3.8 for grade III respectively. PNI was seen in 70% of cases and was a negative prognosticator in terms of DSS and OS on univariate analysis (p =0.033 and 0.042 respectively) and showed a HR of 4.9 on multivariate analysis. Conclusions: Adequate surgical margins, although difficult to achieve, are an important prognosticator. A predominantly tubular histology has the best prognosis, followed by cribriform and solid subtype. The latter can best be considered a high grade malignancy. PNI is a negative prognosticator regardless of named nerve involvement. There is a need for improved adjuvant treatment after surgery in ACC of the head and neck. [Copyright &y& Elsevier]