We previously showed that a native very low-density lipoprotein (VLDL)- and low-density lipoprotein (LDL)-rich mix induces global changes in DNA methylation in cultured THP-1 human macrophages. The exact molecular mechanisms for this response are not yet known. Previous studies showed that apolipoprotein B (ApoB) or its fragments can be localized in nuclei following cellular uptake, thus suggesting that ApoB may have a chromatin-modifying activity. To verify this hypothesis, we assessed whether ApoB epitopes are detected in THP-1 and mouse cell nuclei. Using a combination of immunoblotting, immunocytochemistry and chromatin immunoprecipitation, we showed that ApoB epitopes are present in THP-1 cell and mouse monocyte/macrophage nuclear fractions, but are perinuclear rather than intranuclear. Our results are not consistent with a direct chromatin-ApoB interaction as an underlying mechanism for the observed epigenetic responses to lipoproteins in THP-1 cells.