BACKGROUND: Recent studies have suggested that nuclear lipid droplets (LDs) are organized into domains similar to those of cytoplasmic LDs. As cytoplasmic LDs are formed at the endoplasmic reticulum (ER) membrane, which is structurally continuous with the nuclear envelope, it could be suggested however that nuclear LDs are cytoplamic LDs trapped within an invagination of the nuclear envelope. The resolution of fluorescence confocal microscopy is not sufficiently high to exclude this hypothesis. FINDINGS: We therefore addressed this question by electron microscopy (EM) of serial sections. In human liver tissue, we observed some cytoplamic LDs partly surrounded by the nuclear compartment, but we were also able to identify LDs residing in the nuclear compartment that were not connected to the nuclear envelope. CONCLUSION: These findings indicate that nuclear LDs constitute specific subdomains of the nuclear compartment probably involved in nuclear lipid homeostasis.