Placental isoferritin (PLF) and its unique superheavy chain p43 have been recently described as being synthesized by breast cancer cell lines but not by normal breast epithelial cells. Since previous reports have demonstrated a correlation between the content of 'normal' ferritin in breast cancer tissue and the degree of differentiation and prognosis, we have determined p43 in the cytosol of 122 breast cancer samples by use of the new monoclonal antibody CM-H-9. The synthesis of p43 showed a significantly negative correlation with tumor size (P = 0.0001), histologic grading (P = 0.0038), nuclear pleomorphism (P = 0.0019), rate of mitosis (P = 0.0002), lymphocytic reaction (P = 0.0001) and a significantly direct correlation with estrogen receptor status (P = 0.0009). Although patients with a higher p43 content showed a trend for a better outcome (median follow-up: 61.4 months), an independent influence of the cytosolic p43 content on survival could not be confirmed by a multiple Cox model. Therefore it seems that p43's prognostic impact is linked to the highly significant correlation with features of differentiation although a statistical bias in the Cox model due to the limited number of patients must also be taken into account. On the other hand, the significant correlation of p43 expression with factors for good prognosis was striking and consistent and warrants further research of this tumor product.