Previous studies have proved that a certain acidic isoform of ferritin is specifically synthesized by the placenta and breast-cancer tissue. In this context it has been further reported that the determination of this so-called placental isoferritin (PLF) on the surface of a subset of peripheral lymphocytes is highly specific and sensitive for early stage breast cancer. By use of the monoclonal antibody CM-H-9 and flow cytometry, the levels of placental ferritin (PLF)-positive cells were determined in 133 female patients undergoing surgical excision of a controversial or highly suspicious lesion of the breast detected by mammography. In addition, 61 healthy blood donors served as controls. Values of PLF-positive cells in breast cancer patients differed significantly from those found in women with benign diseases and healthy controls (3.87% vs. 1.55% and 2.02, respectively; p less than 0.00001). Analysis of prognostic factors in breast cancer patients (tumor size, lymph-node status, menopausal status, estrogen receptor status, histologic grading and grading subfactors) revealed significantly higher levels of PLF-positive cells in lymph-node-negative patients compared with node-positive patients (p less than 0.00001). Furthermore, levels of PLF-positive cells showed a significantly negative correlation with tumor size and nuclear polymorphism. In 15 patients who underwent a guide-wire-directed surgical biopsy for a non-palpable, mammographically suspect lesion, 4 cases of cancer correlated with high values of PLF-positive lymphocytes while only 1 patient with a benign histologic result exhibited more than 4% positive cells.