Acute lymphoblastic leukemia (ALL) is characterized by recurrent clonal chromosomal abnormalities, with numerical abnormalities being a common feature especially among children. Case reports in the literature suggest that one such recurrent numerical abnormality is the gain of chromosome 5 (trisomy 5) as the sole abnormality; due to the rarity of these cases, however, little is known about their incidence, clinical features, and prognosis. We have identified seven cases with trisomy 5 as the sole or primary chromosomal abnormality from a total of 3,400 karyotypes collected in the Leukaemia Research Fund UK Cancer Cytogenetics Group Karyotype Database. All cases had a precursor B-cell immunophenotype and there was a male predominance. Five patients were children aged between 7 and 14 years old. Four of the six patients with a reasonable follow-up period had relapsed, indicating a poor prognosis. We conclude that trisomy 5 as the sole numerical abnormality occurs predominantly in older children, may be associated with a poor outcome, and may represent a distinct, albeit rare, cytogenetic subgroup in ALL.