Rare disperse elements (RDEs) have received substantial attention due to their intense application in industry. Sphalerite from some Pb–Zn deposits of MVT, skarn, VMS, SEDEX and epithermal type, containing considerable RDEs contents that could be used as by-product. Here, the concentrations of RDEs in sphalerite from the Dalingkou deposit is examined by in situ laser-ablation inductively coupled mass spectroscopy (LA–ICP–MS), to discuss their substitution mechanism in sphalerite, controlling factors, and genesis model in epithermal system. The Dalingkou deposit is the largest epithermal Ag–Zn–Pb deposit in Zhejiang, South China, with proven reserves of 702 t Ag, 0.10 Mt Pb, 0.15 Mt Zn, and potential resources for RDEs. Orebodies are predominately hosted by intermediate–acid Yanshanian volcanics and subvolcanics and controlled by N–S and NW–SE trending faults. The ores are dominated by abundant base metal sulfides with gangue minerals mainly composed of quartz and rhodochrosite. The hydrothermal activities occurred in four stages: pre-ore stage (stage 1), Pb–Zn mineralization stage (stage 2), Ag–Pb–Zn mineralization stage (stage 3) and post-ore stage (stage 4). Two types of sphalerite were observed (i.e. Sp2 from the stage 2, and Sp3 from the stage 3), according to crosscutting and overprinting relationships of ores. LA–ICP–MS analysis shows that, relative to the Sp3, the Sp2 has higher contents of Fe, Mn, Cd, and In, but slightly lower contents of Ga and Ge. Correlation analyses reveal the incorporation of RDE into sphalerite via both simple substitution, such as Zn2+ ↔ (Cd2+), and coupled substitution, such as 3Zn2+ ↔ In3+ + Sn3+ + □ (vacancy), 3Zn2+ ↔ Ge4+ + 2Cu+, and 2Zn2+↔ (Ag, Cu)+ + Ga3+. Geothermometry of impurity elements (Ga, Ge, In, Mn, and Fe) in sphalerite suggests that the sulfides precipitated from an intermediate- to low-temperature hydrothermal system. It further reveals temperature decrease from stage 2 to stage 3, suggesting fluid mixing between magmatic fluids and meteoric water was involved. Deep parental magma may have contributed In and Cd during the mineralization stage, whereas Ga and Ge were released from surrounding rocks due to hydrothermal alteration, despite that they are not enriched in orebodies. The LA–ICP–MS analysis also reveals that the In, Ga and Ge contents in both Sp2 and Sp3 are too low to be economic. However, compared with sphalerite Cd concentrations from different deposit types worldwide, the Sp2 and Sp3 in Dalingkou have enough high Cd grade as an economic by-product, suggesting that the Dalingkou deposit is also a Cd deposit.