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Rouleaux formation is characterized by the linear “stack-of-coins” aggregation of erythrocytes, resulting from attenuation of the normal electrostatic repulsive forces (zeta potential) between red cell membranes. This reduction in zeta potential is typically mediated by elevated concentrations of plasma proteins, particularly fibrinogen and immunoglobulins, which facilitate intercellular bridging and promote erythrocyte aggregation. Under physiological conditions, the net negative surface charge of erythrocytes, largely conferred by sialic acid residues, promotes mutual repulsion and maintains cells in discrete suspension. The elevation of acute-phase proteins such as fibrinogen in chronic inflammation or infection, and monoclonal or polyclonal immunoglobulin excess in plasma cell dyscrasias and other gammopathies, neutralizes this charge and enables formation of reversible RBC stacks. Importantly, rouleaux formation is reversible and disperses upon saline dilution, a feature that aids in distinguishing it from true immune-mediated agglutination.