Primary cutaneous aspergillosis is a rare, life-threatening, infectious complication in premature infants that may result in fulminant sepsis and subsequent multi-organ failure. In the past decade, the incidence of primary aspergillosis has increased significantly, whereas the high morbidity and mortality of invasive aspergillosis remains unaltered. In vitro studies reveal that more and more Aspergillus species seem to be refractory to the classical treatment with fluconazole or amphotericin B. This case report presents two extremely low birth weight infants (ELBW) with primary cutaneous aspergillosis, which was refractory to amphotericin B. Both patients were successfully treated with systemic voriconazole, an extended-spectrum triazole antifungal, supported by topical care. This paper provides the clinical manifestation, diagnostics and pharmacotherapy of primary cutaneous aspergillosis, as well as pharmacokinetic aspects of voriconazole in ELBW infants.