Background: To our knowledge, there is no direct information on lycopene metabolism in humans. Objective: The objective of this study was to quantify the long-term human bioavailability of lycopene in plasma and skin after a single dose of 14C-lycopene and to profile the metabolites formed. Design: We preselected 2 male subjects as lycopene absorbers and gave them an oral dose of 10 mg synthetic lycopene combined with ≈6 μg [6,6′,7,7′- 14C]lycopene (≈30,000 Bq; 92% trans lycopene). The appearance of 14C in plasma, plasma triacylglycerol-rich lipoprotein (TRL) fraction, urine, expired breath carbon dioxide, and skin biopsies was measured over 42 d. The 14C in lycopene-isomer fractions from plasma and TRL fraction was measured to assess the isomerization of lycopene in vivo. Results: We quantified 14C from 14C-lycopene in plasma, the plasma TRL fraction, expired carbon dioxide, urine, and skin. The time to maximum concentration (tmax) of total 14C-lycopene in plasma was 6 h, and the elimination half-life (t1/2) was 5 d, which were different from the tmax and t1/2 of unlabeled lycopene (0.5 and 48 d, respectively). 14C-Lycopene was extensively isomerized after dosing as a 92% all-trans isomer at dosing but changed to 50% trans, 38% 5 cis, 1%9cis, and 11% other cis isomers after 24 h. A similar pattern of isomerization was seen in plasma TRL fractions. Conclusions: Lycopene was extensively isomerized after dosing and rapidly metabolized into polar metabolites excreted into urine with the rapid peak of 14CO 2 after dosing, which implies that β-oxidation was involved in the lycopene metabolism. Lycopene or its metabolites were detected in skin for up to 42 d.