Asymptomatic hyperprolactinemias associated with altered proportions of molecular forms of circulating prolactin (PRL) have been reported in adults. The scarce references available in children and adolescents prompted us to report our experience in the evaluation and follow-up of patients with macroprolactinemia. We studied 5 patients (1 male and 4 females) aged 11.6–18 years with incidentally discovered asymptomatic hyperprolactinemia. Patients underwent repeated evaluations for a period of 3 months to 8 years, and their PRL levels remained elevated (34.4–516 ng/ml). Structural variants of PRL ≥45 kD ranged between 58.9 and 78.6%. Chromatographic profiles showed increases in Big Big PRL in the 5 cases, ranging between 40 and 72% (normal: 9–21%), and in Big PRL in 3 cases, ranging between 30.0 and 32.6% (normal: 5–25%). Little PRL was decreased in all cases, ranging between 20.6 and 41.1% (normal: 50– 90%). In conclusion, upon detection of hyperprolactinemia with no clinical manifestations and no alteration of the remaining endocrine functions, macroprolactinemia should be considered as a possible diagnosis. The confirmed absence of functional alterations during the follow-up would favor a no-treatment approach and at the same time avoid repeating imaging studies.