Acne vulgaris in infants and children often triggers extensive laboratory evaluation out of concern about associated endocrinopathy. Clinical parameters to help guide evaluation of these children have not been defined. This was a retrospective chart review of 24 preadolescent patients with acne and a review of related medical literature. Two age-related subsets were identified: 12 patients who developed acne before the age of 15 months, 75% male, with comedonal and inflammatory lesions; and 12 patients who developed acne between the ages of 2 and 7 years, 75% female, with primarily comedonal lesions. Laboratory evaluation in 13 of the patients was unremarkable. Bone age was advanced in 1 of the 11 children imaged. Premature adrenarche was diagnosed in four patients; all four had additional clinical signs of puberty and growth parameters >90th percentile. None required additional treatment. Our cohort of preadolescent children presenting with acne included an equal number of patients in two distinct subsets: infantile and childhood-onset acne. Literature review identified a rare third subset presenting with acne, signs of advanced puberty, and associated endocrinopathy. There was no evidence of endocrinopathy in our patients with infantile acne. Two-thirds of our patients with childhood-onset acne had no additional clinical signs of puberty and no evidence of endocrinopathy. A focused history and physical examination is sufficient to evaluate the majority of infants and children with acne. Hand X-ray for bone age is a useful screening test. Further evaluation and endocrinology referral are warranted in preadolescents with acne and advanced bone age or additional clinical evidence of early puberty.