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Acute lymphoblastic leukemia shows marked differences in outcome between children and adults. Since there is limited information on the distribution of clinico-biologic variables in different age cohorts, we analyzed 5202 ALL patients enrolled in the Italian multicenter AIEOP and GIMEMA protocols and stratified them in 9 age cohorts. The highest prevalence of ALL was observed in children, although a second peak was recorded from the 4th decade onwards. Interestingly, the lowest incidence was found in females between 14-40 years, suggesting a protective impact of fertility. Immunophenotypic characterization showed a B-lineage in 85.8% of patients: a pro-B stage, associated to MLL/AF4 positivity, was more frequent in patients between 10-50 years. A T-lineage (14.2%) was rare among small children and increased in 10-40 years patients. The BCR/ABL1 rearrangement increased progressively with age, starting from the 10-14 cohort and impacting for 52.7% of cases in the 6th decade. Similarly, the MLL/AF4 rearrangement constantly increased up to the 5th decade, while the ETV6/RUNX1 rearrangement disappeared from the age of 30 onwards. This study shows that adolescents and young adults are characterized by a male prevalence, greater T-lineage acute lymphoblastic leuekmia percentage, an increase of poor prognostic molecular markers with aging compared to children, and conclusively quantifies the progressive increase with age of BCR/ABL+ patients, potentially manageable by targeted therapies.