PURPOSE: It is difficult at times to differentiate between a papillary carcinoma and benign papilloma of the breast, and papillomas can undergo malignant transformation. The authors investigated the expression of cyclin D1 and MIB-1 to assess the diagnostic value of these markers in distinguishing papillary carcinomas from papillomas of the breast, and in determining the clinical relevance of these markers as prognostic predictors. METHODS: The medical records of 38 patients treated for benign and malignant papillary lesions of the breast at Inje University Pusan Paik Hospital between January 1992 and December 1997 were reviewed. Immunohistochemical stains for cyclin D1 and MIB-1 were performed in 30 cases of papilloma and eight cases of papillary carcinoma of the breast. The authors performed a statistical analysis of the relationship between cyclin D1 and MIB-1 with respect to the size of tumors, pathologic lymph nodes, and postsurgical residual lesions, and the recurrence and survival rates. RESULTS: Breast cancer or ADH was associated with six cases (15.79%) of papillary lesions of the breast. The incidence of postsurgical residual lesions and their recurrence were 2.63% and 2.63% in all the patients with papillary lesions of the breast. The labeling index of cyclin D1 was significantly higher in the eight papillary carcinomas (36.7+/-27.0) than in the 30 papillomas (3.5+/-4.2) (P=0.001). There was a statistically significant difference betweenn the MIB-1 labeling index of the eight papillary carcinomas (4.9+/-5.9) and that of the 30 papillomas (0.4+/-1.4) (P=0.0225). The cyclin D1 and MIB-1 expressions of the single intraductalpapillomas and multiple papillomas were not different. In addition, there was no statistically significant difference of cyclin D1 and MIB-1 in the eight papillary carcinomas with respect to the associated pathologies, size, positive lymph nodes, recurrence or survival. CONCLUSION: These results suggest that cyclin D1 and MIB-1 might be useful markers for distinguishing papillary carcinomas from papillomas of the breast.