The Dingjiashan Pb-Zn deposit (5.35 Mt Pb + Zn @ 1.14% Pb and 4.07% Zn) is hosted by pyroxene-dominated skarn occurring along the contact zones between Proterozoic quartz mica schist and marble in the central Fujian region of southeastern China. The ore genesis of Proterozoic volcanogenic massive sulfide (VMS) vs. Late Mesozoic skarn type has long been debated. In this study, two types of sphalerite (sphalerite I and sphalerite II) were identified based on the mineral assemblages in the sulfide stage of the Dingjiashan deposit. Sphalerite I (including sphalerite Ia and sphalerite Ib subtypes), with a dark gray-blue to black coloring, is predominantly associated with pyrrhotite, whereas sphalerite II (including sphalerite IIa and sphalerite IIb subtypes) shows a light to dark gray-blue coloring and is mainly associated with galena and chalcopyrite. Geological features indicate that sphalerite I predates sphalerite II. Representative time-resolved depth profiles and mapping images based on the LA-ICP-MS method, coupled with inter-element correlation analyses, collectively illustrated that: 1) Fe, Mn, Cd, Co, In, Ga and Ge are present in solid solution; 2) Cu may occur both as solid solution and as micro-inclusions; 3) Ag, Pb and Bi may be intimately associated with galena inclusions hosted by sphalerite. The characteristics of trace and minor elements (such as Fe, Mn, In, Co, Ga, Ge, etc.), along with the results of GGIMFis geothermometer studies, indicate that the main mineralization stage occurred at high-temperature conditions (>300 °C). Compared to Pb-Zn deposits (including 6 VMS deposits and 9 skarn deposits) worldwide, sphalerite from the Dingjiashan Pb-Zn deposit exhibits similar ore-forming temperatures and trace/minor element compositions to those from skarn deposits, but is different to those from VMS deposits. This finding is of great significance for further exploration in the Dingjiashan deposit and—more broadly—the entire central Fujian region. It also provides an important future guide for the differentiation of VMS and skarn deposits.