Background: Apolipoprotein B (apoB) levels in plasma are proportional to the number of all atherogenic, non-high-density lipoprotein (HDL) particles. Non-HDL-C concentration - the aggregate cholesterol carried by apoB-containing particles - is usually highly correlated with apoB levels. This study aimed to describe individuals with discordance between these lipid measures, especially apoB<non-HDL-C discordance, as there are few prior data on this cholesterol-enriched particle phenotype. Methods: We analyzed 2,804 participants of NHANES 2011-2012, a nationally representative US cross-sectional survey with direct apoB and standard lipid fasting measurements. We assigned population percentiles to non-HDL-C and apoB levels and created groups with 5-10 or >10 percentile units of discordantly low apoB (apoB<non-HDL-C: “cholesterol-enriched”) or high apoB (apoB>non-HDL-C: “cholesterol-depleted”). We compared lipids levels and other clinical characteristics across groups. Results: Discordance >5 percentile units was present in 50.9% of individuals. Compared with the cholesterol-depleted group, the cholesterol-enriched phenotype was characterized by a lower prevalence of obesity, diabetes, and hypertension. We found higher levels of low-density lipoprotein cholesterol (LDL-C), non-HDL-C, and HDL-C in cholesterol-enriched compared with cholesterol-depleted groups, whereas triglycerides were similar across groups. Lipid levels were consistent after excluding individuals on lipid-lowering therapy. Conclusion: Despite having higher levels of non-HDL-C and LDL-C, the cholesterol-enriched phenotype had a more favorable cardiovascular risk factor profile compared with the cholesterol-depleted phenotype. Triglycerides were notably low and similar across groups. Evaluation for discordance at both ends of the spectrum may provide additional prognostic information on CVD risk, but further outcomes studies are needed.