To identify genetic loci influencing blood lipid levels in Caribbean Hispanics, we first conducted a genome-wide linkage scan in 1,211 subjects from 100 Dominican families on five lipid quantitative traits: total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), and LDL-C/HDL-C ratio. We then investigated the association between blood lipid levels and 21,361 single nucleotide polymorphisms (SNP) under the 1-logarithm of odds (LOD) unit down regions of linkage peaks in an independent community-based subcohort (N = 814, 42% Dominican) from the Northern Manhattan Study (NOMAS). We found significant linkage evidence for LDL-C/HDL-C on 7p12 (multipoint LOD = 3.91) and for TC on 16q23 (LOD = 3.35). In addition, we identified suggestive linkage evidence of LOD > 2.0 on 15q23 for TG, 16q23 for LDL-C, 19q12 for TC and LDL-C, and 20p12 for LDL-C. In the association analysis of the linkage peaks, we found that seven SNPs near FLJ45974 were associated with LDL-C/HDL-C with a nominal P < 3.5 × 10(-5), in addition to associations (P < 0.0001) for other lipid traits with SNPs in or near CDH13, SUMF2, TLE3, FAH, ARNT2, TSHZ3, ZNF343, RPL7AL2, and TMC3. Further studies are warranted to perform in-depth investigations of functional genetic variants in these regions.