Background. Previous genomic studies revealed phosphotidylinositol-3-kinase (PI3K)/Akt pathway mutation in human salivary gland adenoid cystic carcinoma (ACC). No validation of its prognostic value has been reported. Methods. P-Akt, pan-Akt, phosphorylated-mammalian target of rapamycin (p-mTOR), PI3K, and insulin-like growth factor-1 receptor beta (IGF-1R beta) were detected on 120 salivary gland ACC/adjacent salivary gland pairs immunohistochemically and were correlated with clinicopathological data. Results. Expression of cytoplasmic and nuclear p-Akt, cytoplasmic p-mTOR, nuclear pan-Akt, and nuclear IGF-1Rb were higher in ACC than in adjacent salivary glands. P-Akt, p-mTOR, PI3K, and IGF-1Rb expression were correlated with one another in both cytoplasm and nucleus. Low p-mTOR expression in both subcellular compartments was associated with locoregional recurrence, poor disease-free survival (DFS), and overall survival (OS). Low nuclear p-Akt (Ser473) and p-mTOR expression were independent predictors for poor OS and DFS, respectively. Conclusion. High level of Akt/mTOR activation in ACC is correlated with a significantly improved survival. P-mTOR and nuclear p-Akt are prognostic biomarkers of salivary gland ACC. (C) 2017 Wiley Periodicals, Inc.