Abstract. We cared for a neonate with hyperbilirubinemia requiring phototherapy during the birth-hospitalization, at home, and during two subsequent hospital readmissions. Abnormal red blood cell forms including elliptocytes were seen on his blood film but this failed to explain, to our satisfaction, why his jaundice required such prolonged treatment. Next-generation sequencing, using a panel of 27 genes involved in neonatal jaundice and hemolytic anemia revealed four previously described heterozygous variations, which we postulate resulted in increased bilirubin production from hemolysis, plus retarded bilirubin uptake and conjugation. Mutations were found in the erythrocyte membrane protein band 4.1 gene (EPB41), the alpha-spectrin gene (SPTA1), the gene encoding the enzyme for bilirubin conjugation (UGT1A1), and the gene encoding a transporter of bilirubin from the blood into hepatocytes (SLCO1B1).