It is well known that some of the widely used antibodies directed against hemopoietic antigens exhibit cross-reactivity with normal and neoplastic nonhemopoietic cells. By contrast, relatively little is known about the immunoreactivity of hemopoietic cells with antibodies that detect nonhemopoietic antigens. In this study 43 routinely processed bone marrow biopsy specimens containing infiltrates of acute leukemia of different subtypes were stained with a panel of 20 antibodies that detect nonhemopoietic antigens in formalin-fixed and paraffin-embedded tissue. Thirteen of the antibodies applied (KL1; BMA 120; and antibodies against epithelial membrane antigen, alpha-fetoprotein, prostate-specific acid phosphatase, prostate-specific epithelial antigen, placental alkaline phosphatase, alpha-amylase, serotonin, bombesin, beta-human chorionic gonadotrophin, desmin, and S-100 protein) did not stain blast cells in any of the cases. However, anti-vimentin, HMB45, and anti-myoglobin stained blast cells in the majority of the cases; the antibodies against thyroglobulin, actin, and carcinoembryonic antigen stained blast cells in 10% to 25% of the cases; and anti-neuron-specific enolase stained blast cells in less than 10% of the cases. No correlation was found between the leukemia subtype and the pattern of immunoreactivity. The staining specificity, (i.e., the specificity of binding of the primary antibody--immunologic vs. nonimmunologic binding), was tested by increasing the dilution of the primary antibody and comparing the staining intensity in the bone marrow specimens and control tissue. Staining specificity was confirmed only for staining with the antibodies against neuron-specific enolase and vimentin. The findings show that immunoreactivity of tumor cells in bone marrow biopsy specimens for nonhemopoietic antigens does not exclude a diagnosis of acute leukemia.