Uterine papillary serous carcinoma (UPSC) is a biologically aggressive carcinoma that causes a disproportionate number of endometrial cancer deaths because of its dismal clinical outcome. Although the precursor lesion of UPSC has been suggested both morphologically and molecularly, diagnosis continues to represent a challenge to surgical pathologists, particularly in biopsy specimens, largely in part because of its multiple histologic patterns and many benign morphologic mimics. In this study, we used p53 immunohistochemical staining as an adjunct test to correctly identify six cases of uterine surface carcinoma (USC) prospectively and three cases retrospectively. Both sensitivity and specificity for this immunostaining method approached 100% when the cutoff score of p53 overexpression was 7 or higher. The precision estimated by receiving operating characteristic curve was 100%, indicating that the diagnostic value of the score for p53 overexpression was very high. p53 immunohistochemical staining was considered a significant adjunct diagnostic method for the probable precursor lesion of UPSC. The probable precursor lesion of UPSC, previously referred to as endometrial intraepithelial carcinoma or endometrial carcinoma in situ, appears to represent the early phase of UPSC. However, unlike its names would suggest, this lesion is often multicentric and behaves in a more aggressive fashion than regular in situ carcinomas. For this reason, we prefer the term uterine surface carcinoma, a term that is more descriptive and less restrictive, to emphasize the unique aggressive nature of the UPSC precursor lesion. The reason we postulate using the term uterine surface carcinoma rather than endometrial intraepithelial carcinoma or endometrial carcinoma in situ is that the latter terms would seem define a neoplastic process confined to the endometrial epithelium without potential for metastasis. In reality, the precursor lesion of UPSC has a tendency to stromal and vascular space involvement as seen by the presence of stromal and vascular invasion in one of the prospectively identified USC cases. Therefore, the term uterine surface carcinoma is selected to alert clinicians that this early carcinoma has features of carcinoma in situ, but still carries a potential for metastasis.