Metal inputs to terrestrial ecosystems are of great concern due their toxicity to biota, especially for elements with no biological function such as cadmium. Fast-growing trees such as poplars may have potential in phytoremediation schemes. We assessed accumulation, metal partitioning, gene expression (Pt-HMA4) and overall tolerance to, and interaction between, cadmium (Cd) and zinc (Zn) in Populus trichocarpa 'Trichobel'. We predicted that Zn would have an antagonistic effect in Cd accumulation and anticipated some level of tolerance to these metals. Poplars were grown in sandy substrate under different metal applications, ranging from 1 to 243 mg kg-1 Cd; or 30 to 7,290 mg kg-1 Zn; and also two combined treatments: 27 mg kg-1 Cd with 90 or 270 mg kg-1 Zn. Growth parameters and metal contents in shoots and roots were determined. Transcriptional levels of the Pt-HMA4 gene were assessed in roots and leaves. P. trichocarpa showed a surprisingly high tolerance to Cd, with root biomass being affected only at the highest doses applied. Metals accumulated mainly in roots (up to 6,537 mg kg-1 Cd and 21,500 mg kg-1 Zn), root-to-shoot translocation peaked at the 9 mg kg-1 dose for Cd (41%) and 90 mg kg-1 for Zn (40%). At high Cd/Zn applications, expression of Pt-HMA4 in roots decreased significantly. Contrary to the initial presumption, Zn addition increased Cd uptake, reaching hyperaccumulator-like concentrations in shoots (≥ 100 mg kg-1 Cd). Differential root-to-shoot partitioning has a major role in Cd tolerance in P. trichocarpa; partly by down-regulating the Pt-HMA4 gene in roots. Zn addition promoted high Cd uptake without any detriment to plant growth. P. trichocarpa was tolerant to extreme Cd concentrations, offering a great potential to be used in phytoremediation techniques for stabilization/extraction of Cd from soils contaminated by both Cd and Zn.