Zircon grains in rocks collected from the Itsaq Gneiss Complex, southwest Greenland, were analyzed for U–Pb and Lu–Hf in the same grain using isotope dilution – thermal ionization mass spectrometry (TIMS) and multicollector – inductively coupled plasma – mass spectrometry (MC–ICP–MS). Grains were pretreated using chemical abrasion or air abrasion to assure that only zircon material unaffected by the migration of parent and daughter elements was analyzed. The data are consistent with derivation of all studied rocks from a single enriched mantle source or mafic crustal protolith with 176Lu/177Hf of 0.022 ± 0.003 that was repeatedly melted and produced tonalitic magmas. The assessment of the primary mantle source from which this mafic protolith was derived, at or before 3.85 Ga, greatly depends on the assumed composition of the bulk silicate Earth. Using the currently accepted Lu–Hf bulk Earth parameters based on the analysis of chondrites yields εHf(T) of 0 to +1 for the 3.80–3.86 Ga rocks, suggesting that the protolith was derived from mantle that underwent moderate depletion shortly before 3.9 Ga. However, using alternative models of the bulk silicate Earth composition, i.e., that account for the possible irradiation-induced accelerated decay of 176Lu in the early Solar System, and (or) loss of the products of early planetesimal or planetary differentiation, can lead to widely variable interpretations of the enrichment or depletion history of the mantle source of the Itsaq protolith.