Lead (Pb) and arsenic (As) are potentially toxic in their most reactive forms, but can also occur as structural and specifically adsorbed (more stable forms) ions on clay minerals. Due to their lower mobility in soils, structural and specific adsorbed forms are usually neglected in environmental studies, but can be important, for example, in geochemistry researches. The aim of this study was to evaluate the occurrence of stable forms of Pb and As in the clay fraction of soils in a region rich in Pb ore (galena) in south Brazil using more aggressive sequential extractions (boiling 5 mol L−1 NaOH, successive citrate-bicarbonate-dithionite steps, and sodium bisulfate fusion). X-ray diffraction was used to follow possible mineralogical variations after each sequential extraction. We sampled soils from two areas rich in trace elements, with high occurrence of mineral deposits (PbS) in carbonate and phyllite/mica schist rocks. A reference soil formed on mineralized granite/gneiss was also sampled. In different mineral phases of the sequential extraction, preferential association of Pb with minerals extracted by 5 mol L−1 NaOH (kaolinite, low crystalline smectite and precipitated of Pb-S and Pb-P) was observed. In soils formed from parent materials at the phyllite/mica schist metamorphic stage, Pb contents solubilized by NaOH were extremely high (maximum> 28,000 mg kg−1). Lead exists in the mineral structure, such as Fe oxides, as result of the isomorphic substitution of Fe for Pb. Manganese oxides were also important host of Pb in the clay fraction. The largest As contents occurred at greater depth in the soil. The more aggressive sequential extraction procedure is more suitable to estimate the structural and specific adsorbed forms of Pb and As in clay minerals.