Chondrite-normalized rare earth element (REE) plots of whole-rock geochemical analyses are commonly used to describe the history of magmatic systems. In the particular case of porphyry copper deposits, which are produced by ore-forming magmatic-hydrothermal systems, whole-rock REE concentrations commonly show an unusual depletion in the final phase of magmatism associated with the main ore-forming stage. Interpretation of REE signatures requires establishing whether they result from magmatic or hydrothermal fractionation processes, or a combination of both. We investigated whole-rock trace-element and REE patterns of samples from the giant Ok Tedi porphyry copper-gold deposit, Papua New Guinea, and found that REEs were most depleted in zones of greatest hydrothermal alteration. REE-rich accessory phases zircon, apatite, and titanite have lower modal abundances and become smaller and more anhedral in these intensely altered zones as compared to less altered rocks. This mineralogical change is accompanied by depletions in P, Ti, Y, and Zr, and deviations of Zr/Hf and Y/Ho from chondritic trace-element ratios—chemical signatures indicative of hydrothermal fractionation. We conclude that destruction of REE-rich accessory minerals, particularly apatite, has led to hydrothermal remobilization and depletion of REEs. This implies that intrusive rocks that experienced high-salinity, oxidized fluid-rock interaction at temperatures >400°C may have had their original magmatic REE signature modified.