The diagnosis of leukemia cutis and distinction of early myeloid cells and blasts from lymphoblasts or other lymphoid cells can be difficult, particularly if only fixed tissue is available. O13, a monoclonal antibody that recognizes CD99, the p30/32MIC2 gene product, has been used to identify a number of cell types, including lymphoblasts, in paraffin sections. To evaluate the usefulness of CD99 immunoreactivity in the diagnosis of leukemia cutis, we analyzed cases of cutaneous involvement by acute lymphoblastic leukemia/lymphoblastic lymphoma and acute myelogenous leukemia for the presence of this marker. Without the use of antigen retrieval methods, lymphoblasts in cases of cutaneous involvement by acute lymphoblastic leukemia/lymphoblastic lymphoma were immunoreactive for CD99 in 9 of 9 cases. Myeloblasts and early myeloid cells in cases of cutaneous involvement by acute myelogenous leukemia were immunoreactive for CD99 in 12 (80%) of 15 cases. We conclude that CD99 is a sensitive but nonspecific marker for cutaneous involvement by acute lymphoblastic leukemia/lymphoblastic lymphoma and that CD99 is immunoreactive in the vast majority of cases (21 [88%] of 24 cases) of leukemia cutis.