The hematologic, cytomorphologic, and cytogenetic features of 50 cases of leukemia cutis (LC), occurring in 40 patients, are presented. The patients’ ages ranged from 19 to 75 years (mean, 42 years). The primary hematologic diagnoses in these patients included acute nonlymphoblastic leukemia (ANLL), 13 patients; myelodysplastic syndrome (MDS), 19 patients; chronic lymphocytic leukemia, 3 patients; chronic granulocytic leukemia, 3 patients; and polycythemia vera, 1 patient. Leukemia cutis developed in one patient without any known prior or subsequent hematologic disorder. The 13 cases of ANLL included French–American–British types M1 (1 case), M2 (5 cases), M3 (1 case), M4 (5 cases), and M5 (1 case). Leukemia cutis preceded blood and/or bone marrow manifestations of leukemia in nine patients with MDS and one with ANLL. The interval from skin biopsy to systemic leukemia ranged from 3 weeks to 20 months (mean, 6 months). In seven patients with MDS and three patients with ANLL, LC occurred concomitantly with leukemic transformation. Only two patients with MDS and LC did not have progression to acute leukemia during the 20 and 24 months they have been observed. Diagnoses other than LC initially were considered in five of the patients. LC was characterized most often by a dense mixed cellular dermal infiltrate that circumscribed vascular and adnexal structures. Nine patients with MDS (47%) and one with ANLL (8%) had complex chromosomal abnormalities in their bone marrow samples at the time of LC. This article reports the occurrence of LC in patients with MDS and suggests that LC is an early manifestation of leukemic transformation in these patients. These results may be important in identifying high-risk patients for early interventional therapy.