Vesiculopustular exanthemas are common in newborns, usually benign and self-limiting, but may also indicate infections or congenítal/hereditary disorders. We report a 5-year-old boy who presented at birth with erythrotlerma and generalized bullous lesions, initially suggestive of transient neonatal pustular melanosis. The rash persisted, forming abscesses, and required hospitalization at 10 days of age. Serology excluded neonatal HSV, congenital syphilis, and HIV; while vesicle cultures grew Staphylococcus aureus. Lesions responded to antibiotics but recurred after discontinuation. Other differential diagnoses, including eosinophilic pustular folliculitis and leukocyte adhesion deficiency type 2 (LAD2), were excluded. Oral antibiotic prophylaxis and topical therapy controlled pyoderma; however, recurrent pulmonary infections, non-infections gastroenteritis, and maculopapular rashes developed. By 2 years of age, multiple food allergies were diagnosed, and total IgE was markedly elevated. Genetic testing at 2.5 years confirmed a heterozygous pathogenic STAT3 mutation, establishing autosomal dominant hyper-IgE syndrome (AD-HIES, Job syndrome). Progressive scaphocephaly developed, requiring biparietal decompression surgery at 3.5 years. At 5 years, antibiotic prophylaxis remains necessary, and seasonal IVIG therapy has effectively reduced pulmonary infections despite normal IgG levels. This case highlights a rare cause of neonatal pustular dermatosis. Hyper-IgE syndrome should be considered even when persistent pyoderma is the sole early manifestation, as skeletal and immunologic complications often appear later. Early recognition facilitates timely, targeted management.  Kulcsszavak: neonatal skin lesion, vesiculopustular exanthema, newborn, AD-HIES, autosomal dominant hyper-IgE syndrome