AbstractBackgroundCarcinoma ex pleomorphic adenoma (CXPA) is an aggressive, poorly understood salivary gland malignancy. Misdiagnosis is common, because the residual mixed tumor component may be small, and various carcinoma subtypes are possible.MethodsWe retrospectively reviewed the medical records of 73 patients with major salivary gland CXPA treated at our institution from 1960 to 1994. Of the 73 patients, 66 had primary tumors and 7 had recurrent tumors; 47 were men, and 26 were women; the mean age was 61 years.ResultsAdenocarcinoma (31 cases) and salivary duct carcinoma (24 cases) were the most common malignant subtypes. All patients were treated surgically, and 32 also had radiation therapy. Of 66 patients with primary tumors, 23% had local recurrence. Metastasis (either initial or delayed) occurred regionally in 56% and distantly in 44%. Thirty‐six patients (55%) died of the disease. At 3 years, overall survival was 39% and at 5 years, 30%.ConclusionsImportant prognostic factors include tumor size, grade, and clinical and pathologic stage. Patients with minimally invasive tumors (<5 mm) should do well with appropriate surgical treatment. © 2001 John Wiley & Sons, Inc. Head Neck 23: 705–712, 2001.