Abstract: To analyze the effect of possible risk factors, including breastfeeding, on the development of childhood-onset psoriasis, a multicenter case-control study with prospective collection of data was performed. Using a standard questionnaire, personal and specific variables including family history of psoriasis, maternal and environmental tobacco smoke exposure, body mass index (BMI), exclusive and partial breastfeeding for at least 3 and 12 months, cow’s milk intake before 1 year, birth delivery method, and stressful life events were collected during 2009 from 537 patients with psoriasis and 511 controls younger than 18. Overall, patients more frequently reported exposure to environmental tobacco smoke at home and stressful life events in the year preceding the diagnosis than controls. The odds ratios (OR) for smoking and stressful life events were 2.90 (95% confidence interval [CI] = 2.27–3.78) and 2.94 (95% CI = 2.28–3.79), respectively. In addition, children with psoriasis were more likely to have a higher BMI (>26) than controls (OR = 2.52; 95% CI = 1.42–4.49). High BMI, environmental tobacco smoke exposure at home, and stressful life events may influence the development of pediatric psoriasis.