In the interpretation of the varied and complex cytogenetic counts obtained in analysis of bone marrow (BM) samples for leukemia, loss or gain of certain chromosomes may or may not be significant for prognosis. Loss of the Y chromosome in elderly males is a benign finding. Trisomy 15 is rare and may represent another age-related abnormality, particularly in males, together with -Y. We reviewed 3,242 routine referrals sent to our laboratory for BM cytogenetics, over a period of 34 months. We detected 5 cases with uncomplicated trisomy 15, 3 in males and 2 in females. Three of these patients had the diagnosis of myelodysplastic syndrome (MDS). All 3 males showed a -Y cell line, although the 2 females did not have an X chromosome loss. All 5 patients were alive and well at times varying from 12 months to 4 years post-diagnosis. In the further analysis of our referral cohort, there were 62 males with loss of the Y chromosome as the sole abnormality, and of these 47 (76%), were referred with myeloid disease. The frequency of trisomy 15 in our laboratory was 1/475 referrals, but 1/292 in successful cultures from new patients. This is the first report providing frequency data for trisomy 15. Further data with longer term follow-up is required to establish the significance of trisomy 15 in elderly leukemic patients.