Collodion membrane in the neonate may be the initial presentation of a number of different conditions. There is a lack of data correlating the extent of clinical involvement to the underlying disease and prognosis. We sought to identify features predictive of the final outcome and complications in a cohort of patients with collodion membrane, using a disease severity score. This was a retrospective cohort study of newborns with collodion membrane at a tertiary care institution over a period of 31 years. We designed and applied a 0- to 15-point severity score and correlated the results with the final diagnoses and complications. Data on demographics, membrane shedding, and treatment were collected. We identified 29 cases. Congenital ichthyosiform erythroderma and lamellar ichthyosis were the most common final diagnoses with 7 of 29 cases (24%) each; 3 patients were given the diagnosis of a syndromic ichthyosis. The classic nonsyndromic ichthyoses had higher average score results (7.33) than the syndromic ichthyoses (2.0) and other presentations (4.0), (P= .0097). Patients with major complications had higher, but nonsignificant, average severity scores (P= .64). The retrospective design and small number of patients with a syndromic ichthyosis are limitations. Prospective studies are required to validate the proposed disease severity score.