Deletion 20q is a common chromosomal abnormality in myeloid neoplasms. Detection of del(20q) in patients following cytotoxic therapies raises concerns for an emerging therapy-related myeloid neoplasm. In this study, we identified 92 patients who acquired isolated del(20q) in their bone marrow following cytotoxic therapies for malignant neoplasms. Seventy-six patients showed interstitial and sixteen patients showed terminal 20q deletion. The median interval from prior cytotoxic therapies to detection of del(20q) was 58 months (range, 5-213 months). With a median follow-up of 23 months (range, 1-183 months), 21 (23%) patients developed therapy-related myeloid neoplasm and 71 (77%) patients did not. In patients who developed therapy-related myeloid neoplasm, del(20q) presented in a higher percentage of metaphases (60 vs 25%, P<0.0001); persisted for a longer period of time (24 vs 10 months, P=0.0487); and was more often a terminal deletion (33 vs 13%, P=0.0006) compared with patients who did not develop therapy-related myeloid neoplasm. Clonal evolution was only detected in patients with therapy-related myeloid neoplasm (4 patients, 19%). We conclude that del(20q) emerging after cytotoxic therapy represents an innocuous finding in more than two-thirds of patients. In patients who develop a therapy-related myeloid neoplasm, del(20q) often involves a higher percentage of metaphases, persists longer and more frequently is a terminal rather than an interstitial deletion.