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Background. Recently, the authors reported that membrane-associated phospholipase [A.sub.2] (M-[PLA.sub.2]) was one of the acute phase reactants and increased in serum of patients with various malignant tumors. Methods. M-[PLA.sub.2] concentrations in tissue specimens from 78 breast cancers, 16 benign breast tumors, and 10 normal breast tissues were determined by a specific radioimmunoassay recently developed. Immunohistochemical staining was performed on all specimens by the avidin-biotin-peroxidase method. Results. Tissue levels of M-[PLA.sub.2] concentration were significantly higher in breast cancer than in benign breast tumor or normal breast tissue (P < 0.01). Correlation analyses between the tissue concentration of M-[PLA.sub.2] and clinicopathologic factors showed that tissue M-[PLA.sub.2] levels were significantly higher in patients with skin or muscle invasion, vessel involvement, and distant metastasis than in those without. In addition, this enzyme concentration was significantly greater in scirrhous carcinoma than in papillotubular or solid-tubular carcinoma. No association was found between M-[PLA.sub.2] concentration and steroid hormone receptor status. Immunohistochemically, M-[PLA.sub.2] was preferentially stained in the invading zone of breast cancer tissues, especially in scirrhous carcinoma. Patients with breast cancer with low levels of M-[PLA.sub.2] showed significantly longer overall survival and disease-free survival compared with those with high levels of this enzyme at the cutoff point of 50 ng/100 mg protein. The combination of estrogen receptor status with M-[PLA.sub.] concentration could be a powerful prognostic factor in predicting such survival rates. Conclusions. M-[PLA.sub.2] is closely related to the malignant potential of breast cancers, and the M-[PLA.sub.2] contents in breast cancer tissues could be a new valuable prognostic factor, other than the hormone receptor, in delineating the status of human breast cancer. Cancer 1993; 71:3058-64.