Abstract: To discuss the expression and location of the transcription factor Fra-1 in benign and malignant human breast tissues. Methods: Fra-1 expression was investigated immunohistochemically in neoplastic breast diseases ranging from benign fibroadenomas to very aggressive undifferentiated carcinomas. The correlation between Fra-1 expression and other indicators of breast carcinoma prognosis ( ER, PR, and ErbB2 receptors ) were analyzed. Results: The nuclei of all neoplastic breast tissue cells, both in benign and malignant breast tissues, were immunoreactive to anti-Fra-1 antibodies. In 85% of the benign tumors ( 17/20 ), the immunoreactivity of the anti-Fra-1 antibodies was exclusively restricted to the nuclei. In three cases ( 3/20, 15% ), focal unequivocal cytoplasmic staining was also observed. Strong positive nuclear staining for Fra-1 was easily seen in all types of breast carcinomas. However, concomitant nuclear-cytoplasmic immunoreactivity was observed in all types of breast carcinomas. A clear shift in Fra-1 immunoreactivity, from an exclusively nuclear to a simultaneous nuclear and cytoplasmic localization, was observed in 90.2% ( 37/41 ) of breast carcinomas. No inverse relationship was observed between Fra-1 and the ER and PR protein levels in the malignant tumors. The relative Fra-1 expression level was not correlated with ErbB2 expression. Conclusion: The overall expression, pattern, and intensity of the Fra-1 protein were correlated with breast oncogenesis. Fra-1 overexpression, leading to persistently high cytoplasmic accumulation, may play a role in breast carcinogenesis.