Contrary to the major vitamin E congener α-tocopherol, which carries a saturated sidechain, and α-tocotrienol, with a threefold unsaturated sidechain, little is known about the intracellular fate of α-tocomonoenol, a minor vitamin E derivative with a single double bond in C11′-position of the sidechain. We hypothesized that, due to structural similarities, the uptake and metabolism of α-tocomonoenol will resemble that of α-tocopherol. Cytotoxicity, cellular uptake of α-tocomonoenol, α-tocopherol and α-tocotrienol and conversion into the short-chain metabolites αCEHC and αCMBHC were studied in HepG2 cells. α-Tocomonoenol did not show significant effects on cell viability and its uptake was similar to that observed for α-tocopherol and significantly lower than for α-tocotrienol. α-Tocomonoenol was mainly metabolized to αCMBHC in liver cells, but to a lower extent than α-tocotrienol, while α-tocopherol was not metabolized in quantifiable amounts at all. In summary, the similarities in the cytotoxicity, uptake and metabolism of α-tocomonoenol and α-tocopherol suggest that this minor vitamin E congener deserves more attention in future research with regard to its potential vitamin E activity.