AbstractCopy number increase (CNI) of ACTN4 has been associated with poor prognosis and metastatic phenotypes in various human carcinomas. To identify a novel prognostic factor for salivary gland carcinoma, we investigated the copy number of ACTN4. We evaluated DNA copy number of ACTN4 in 58 patients with salivary gland carcinoma by using fluorescent in situ hybridization (FISH). CNI of ACTN4 was recognized in 14 of 58 patients (24.1%) with salivary gland carcinoma. The cases with CNI of ACTN4 were closely associated with histological grade (P = 0.047) and vascular invasion (P = 0.033). The patients with CNI of ACTN4 had a significantly worse prognosis than the patients with normal copy number of ACTN4 (P = 0.0005 log‐rank test). Univariate analysis by the Cox proportional hazards model showed that histological grade, vascular invasion, and CNI of ACTN4 were independent risk factors for cancer death. Vascular invasion (hazard ratio [HR]: 7.46; 95% confidence interval [CI]: 1.98–28.06) and CNI of ACTN4 (HR: 3.23; 95% CI: 1.08–9.68) remained as risk factors for cancer death in multivariate analysis. Thus, CNI of ACTN4 is a novel indicator for an unfavorable outcome in patients with salivary gland carcinoma.