We analyzed the clinicopathologic and molecular findings in 26 adults (age 16-72 years) with T-cell acute lymphoblastic leukemia (T-ALL) and observed features that correlated with age. Patients older than 60 years (n = 5) had a low frequency of hepatosplenomegaly (0 [0%]), anterior mediastinal mass (1 [20%]), and lymphadenopathy (2 [40%]), and completely responded to chemotherapy (4 of 4). The T-ALL in this group commonly expressed myeloid antigens (4 [80%]), had lineage-inappropriate gene rearrangements (2/3 [67%]) and chromosome 2 deletion (3/4 [75%]), and exclusively used the V(III) or V(IV) families of the T-cell receptor (TCR) gamma gene. In comparison, patients 16 to 60 years old (n = 21) more commonly had an anterior mediastinal mass (8 [38%]), hepatosplenomegaly (10 [48%]), and lymphadenopathy (16 [76%]). The tumors in these patients commonly used the TCR gamma gene VI or V(II) families (17/25 total rearrangements [68%]). Myeloid antigen expression (5 [24%]) and lineage inappropriate gene rearrangements (4/15 [27%]) were uncommon. Within this group, CD1a expression correlated with age 28 to 60 years. These results illustrate considerable age-related heterogeneity in adult T-ALL, which may reflect differences in tumor cell maturation.