Two patients with numerous hand mirror cells in the bone marrow were investigated by morphologic, cytochemical, immunohistochemical, flow cytometric, cytogenetic, and gene rearrangement analysis. Both demonstrated a mixed immunophenotype with expression of myeloid and T-lymphoid features. Interestingly, both strongly expressed CD2 (adhesion molecule) and CD7. Review of the literature uncovered additional cases of acute mired leukemia-hand mirror variant with strong expression of CD2, CD7, and CD11b, suggesting a unique subset. Under normal physiologic conditions lymphoid cells and monocytes assume a hand min-or configuration when adhesion molecules (i.e., CD2, CD11b) are triggered by their corresponding ligands. Evidently not all acute leukemias with surface adhesion molecules form hand mirrors, which suggests an additional stimulatory event. The presence of adhesion molecules on these activated cells is important to homing, trafficking, spread of the malignant cells, clinical course, prognosis, and treatment. Therefore all HMC cases require detailed analysis to ensure accurate diagnosis. In-depth evaluation of such cases should give new insights into clinical presentation, prognosis, and treatment of these unusual cases.