Identify variables that are independent predictors of survival in carcinoma ex pleomorphic adenoma (CXPA) of the major salivary glands using a population-based database and evaluate the incidence and management strategies for this rare malignancy. The Surveillance, Epidemiology, and End Results (SEER) database was queried for all cases of major salivary gland CXPA from 1973 to 2015. Of the 619 patients identified, the parotid gland was the most common site of involvement (76.9%, 476/619). The reported incidence of CXPA has risen in the past decade (2005-2015, 0.24 to 0.63 per 1,000,000). The 2-year and 5-year disease-specific survival (DSS) rates were 90.3% and 80.4%, respectively. On univariate analysis, facial nerve sacrifice was not a statistically significant predictor of survival (HR = 1.213, 95% CI [0.588-2.058], P = 0.602). Patients with a tumor size >4 cm, multiple positive lymph nodes, and distant metastatic disease had a 2 to 4-fold statistically significant increase in mortality using a multivariate analysis. Statistical significance was not demonstrated in the DSS of patients who underwent partial versus total parotidectomy procedures. CXPA is a rare salivary malignancy that has a reported increased incidence in the last decade. Tumor size >4 cm, multiple positive lymph nodes, and distant metastatic disease are predictors of disease-specific mortality. Further research should be conducted to improve early detection and survival strategies for this salivary cancer. 4.