The current understanding of the genetic architecture of lipids has largely come from genome-wide association studies (GWAS). To date, few GWAS have examined the genetic architecture of lipids in Polynesians, and none have in Samoans, whose unique population history, including many population bottlenecks, may provide insight into the biological foundations of variation in lipid levels. Here we performed a GWAS of four fasting serum lipid levels: total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TG) in a sample of 2849 Samoans, with validation genotyping for associations in a replication cohort comprising 1798 Samoans and American Samoans. We identified multiple genome-wide significant associations (P?5?×?10-8) previously seen in other populations—APOA1with TG, CETPwith HDL, and APOEwith TC and LDL—and several suggestive associations (P?1?×?10-5), including an association of variants downstream of MGAT1and RAB21with HDL. However, we observed different association signals for variants near APOEthan what has been previously reported in non-Polynesian populations. The association with several known lipid loci combined with the newly identified associations with variants near MGAT1and RAB21suggest that while some of the genetic architecture of lipids is shared between Samoans and other populations, part of the genetic architecture may be Polynesian-specific.