The Fule deposit is a typical Cd-, Ge- and Ga-enriched Pb-Zn deposit located in the southeast of the Sichuan–Yunnan–Guizhou Pb-Zn polymetallic ore province in China. Zoned, euhedral cubic and pentagonal dodecahedral and anhedral pyrites were observed, and they are thought to comprise two generations. First generation pyrite (Py1) is homogeneous and entirely confined to a crystal core, whereas second generation pyrite (Py2) forms bright and irregular rims around the former. Second generation pyrite also occurs as a cubic and pentagonal dodecahedral crystal in/near the ore body or as an anhedral crystal generally closed to the surrounding rock. The content of S, Fe, Co, and Ni in Py1 are from 52.49 to 53.40%, 41.91 to 44.85%, 0.19 to 0.50% and 0.76 to 1.55%, respectively. The values of Co/Ni, Cu/Ni and Zn/Ni are from 0.22 to 0.42, 0.02 to 0.08 and 0.43 to 1.49, respectively, showing that the Py1 was formed in the sedimentary diagenetic stage. However, the contents of S, Fe, Co, and Ni in Py2 are in the range from 51.67 to 54.60%, 45.01 to 46.52%, 0.03 to 0.07% and 0.01 to 0.16%, respectively. The Co/Ni, Cu/Ni and Zn/Ni values of Py2 are from 0.40 to 12.33, 0.14 to 13.70 and 0.04 to 74.75, respectively, which is characterized by hydrothermal pyrite (mineralization stage). The different δ34S values of the Py1 (−34.9 to −32.3‰) and the Py2 (9.7 to 20.5‰) indicate that there are at least two different sources of sulfur in the Fule deposit. The sulfur in Py1 was derived from the bacterial sulfate reduction (BSR), whereas the sulfur in the ore-forming fluids (Py2) was derived from the thermochemical sulfate reduction (TSR). The main reasons for the different morphologies of pyrite in the regular spatial distribution in the Fule deposit are temperature and sulfur fugacity.