The differentiation of intraductal papilloma (IDP) in the breast from ductal carcinoma in situ (DCIS) is sometimes difficult. Fifty papillary lesions (25 DCIS and 25 IDP) were immunohistochemically examined using a panel of antibodies, including CK5/6, ER, p63, Ki‐67, chromogranin A, synaptophysin, neuron specific enolase, CD56, MUC1, MUC3, CD44, p21, p27, and p53. The immunohistochemical staining pattern of each antibody was evaluated using the Allred scoring system. Then, the area under curve (AUC) for each antibody was computed by receiver operating characteristic (ROC) analysis. DCIS typically showed high scores for ER and MUC3 reactivity compared with IDP, and the AUC for ER and MUC3 were 0.941 and 0.908, respectively. In contrast, IDP showed high scores for CK5/6 and p63 reactivity compared with DCIS, and the AUC for CK5/6 and p63 were 1.00 and 0.954, respectively. We devised a ‘Differential Index’ (DI) using the following formula: [S(ER) + S(MUC3)]/[S(CK5/6) + S(p63) + 1]. The distributions of the DI for IDP and DCIS did not overlap when the cutoff value was placed arbitrarily at DI = 1.0. From these results, it is concluded that a panel of four CK5/6, ER, p63, and MUC3 antibodies provide valuable information for differentiating IDP from DCIS.

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