Diagenetic pyrite from the Silurian continental red bed-hosted Transfiguration cupriferous deposit in the Quebec Appalachians, Gaspé Belt, Canada, contains up to ∼2% (m/m) Pb. This large Pb content in pyrite contrasts with experimental determinations that indicate solubility of <0.1% (m/m) PbS in pyrite at high temperature. The distribution of Pb in pyrite is heterogeneous, with plumbiferous domains occurring as patches and concentric growth layers alternating with Mn- and Mo-bearing zones. The plumbiferous pyrite is surrounded by As- and Cu-rich rims. This compositional heterogeneity, however, is elusive under normal backscattered-electron (BSE) imaging, but it can be recognized under high-gain BSE. Proton-induced X-ray emission (PIXE) confirms the presence of Pb. Plumbiferous pyrite with >0.1% (m/m) Pb has rarely been described; it is thus possible that plumbiferous pyrite may have been overlooked in metalliferous deposits worldwide. The plumbiferous pyrite from Transfiguration has a light S-isotope composition that is characteristic of bacterial sulphate reduction. We suggest that Pb in diagenetic pyrite indicates Pb-tolerant bacterial activity and, perhaps, constitutes a biosignature of bacterial tolerance to Pb in ancient sedimentary systems.