Paget's disease of the nipple is often found in conjunction with underlying ductal carcinoma in situ (DCIS). In isolation, Paget's disease of the nipple, like DCIS, confers an excellent prognosis for survival. Our objective was to determine if Paget's disease identified with synchronous parenchymal DCIS has as favorable an outcome as Paget's disease alone. We analyzed a prospectively maintained pathology database and medical records to identify all patients diagnosed with Paget's disease of the nipple between June 1996 and December 2011. Overall survival was analyzed using Kaplan-Maier statistics and Cox proportional hazards modeling. Seventy-four patients were identified with Paget's disease: five (6%) with isolated Paget's of the nipple, 22 (30%) associated with parenchymal DCIS, and 47 (64%) associated with invasive cancer (± DCIS). Unexpectedly, patients with Paget's disease and DCIS had a worse prognosis than those with Paget's disease alone. Survival correlated with pathologic stage at diagnosis. Among the 16 deaths, median survival was 2.8 years (range, 0.1 to 15.2 years). Median follow-up for the entire cohort was 4.2 years (range, 0.1 to 15.2 years). Thus, Paget's disease with parenchymal DCIS may confer worse survival than isolated Paget's disease of the nipple, suggesting the difficulty of identifying invasive carcinoma within a background of DCIS.