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* Context.--The lung is the most common site of metastasis during the natural history of malignant tumors. Breast carcinoma has a propensity for distant metastasis, and the lung and pleura are among the most common metastatic sites. Although it is often difficult to make a clear-cut differential diagnosis between the two, distinguishing primary lung carcinoma from breast carcinoma metastatic to the lung is important because the treatment modalities are different. Objective.--To elucidate the utility of mammaglobin and gross cystic disease fluid protein 15 (GCDFP-15), which are known to be breast-specific antigens, in distinguishing various primary lung and pleural tumors from breast carcinoma metastasizing to the lung. Design.--A total of 20 cases of breast carcinoma metastatic to the lung and 263 tumors of nonbreast origin located in the lung and pleura were analyzed. Results.--Of the 20 cases of breast carcinoma metastatic to the lung, 10 (50.0%) were immunoreactive for mammaglobin and 9 (45.0%) for GCDFP-15, the frequency of positivity being slightly higher for the former than for the latter. The area immunopositive for mammaglobin showed more diffuse staining than the area immunopositive for GCDFP-15. Furthermore, the specificity of mammaglobin for breast carcinoma metastatic to the lung was superior (98.9%) to that of GCDFP-15 (91.8%). Conclusion.--The sensitivity of mammaglobin is equal or superior to that of GCDFP-15 for investigation of breast carcinoma. Immunopositivity for mammaglobin is more diffuse than that for GCDFP-15. In terms of practical diagnosis, mammaglobin immunohistochemistry can serve as a differential marker of breast carcinoma and should be added to the immunohistochemical panel., The lung is the most common site of metastasis during the natural history of malignant tumors. (1) In particular, breast carcinoma has a propensity for distant metastasis, and the lung [...]