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An antigen-dependent negative selection blood cell separation method is described. Rare circulating epithelial cells can be separated from blood by depleting erythrocytes from a blood sample. Erythrocytes are depleted by agglutination. The new method comprises the use of an agglutinating agent, such as an anti-glycophorin A or glycophorin B antibody, as glycophorin A or B are present on erythrocytes and not on the desired epithelial cells. With regular mixing, desired rare circulating epithelial cells do not become entrapped in the red cell agglutinate.