Background: Chanarin-Dorfman syndrome is a rare autosomal recessive disease characterized by accumulation of triglycerides in cells from multiple organs. Its exact prognosis is not well known because of a lack of case series. It is often treated using oral retinoid but risk-benefit ratio of this drug has not been properly studied. Objective: To improve the management of patients by bringing new clinical, molecular and therapeutic data. Methods: Large retrospective multi-center observational research study performed by international expert centers combined with a comprehensive literature search. Results: A total of 38 patients were included. Molecular analysis revealed 19 different mutations including 7 unreported previously. Clinical data and follow-up data were available for 31 patients (median follow-up: 8 years (range: 0 – 38 years)). Skin anomalies (mild to severe ichthyosis) were present in all patients. Liver abnormalities (including 3 cirrhosis) were the most frequent extracutaneous change (28 patients). A total of 17 of the 31 patients received oral retinoids during a median duration of 7.9 years (range: 0.5 – 19.1 years) and one had cirrhosis diagnosed during treatment. Limitations: Retrospective design. Difficulty of comparison with the previously published data because of a lack of standardized reporting outcomes. Conclusion: The risk-benefit ratio appears to be in favor of the use of oral retinoids in cases with severe cutaneous disease.