The Surficial Geochemistry Case Studies Project in the Lake Nipigon region involved detailed Quaternary mapping and multimedia geochemical sampling within five case study areas. Two of these areas, Lac des Iles and Tib Lake, contain known platinum group element (PGE) mineralization. The other three case study areas feature drainage catchments with lakes that contain anomalous levels of PGEs in bottom sediment. Surficial media sampled included till, soils, stream sediment, lake sediment, peat, surface water, and groundwater. Over Archean terrain, such as at Lac des Iles and Tib Lake, there is excellent geochemical contrast between the PGE prospective rock type (mafic to ultramafic intrusive) and the surrounding rock type (e.g., granitoid rocks). This geochemical contrast is mirrored in the geochemistry of most surficial media sampled during this project. Over the Nipigon Embayment, the geochemical contrast between mafic and ultramafic rocks (e.g., “Seagull”-type intrusions) and the surrounding diabase sill rocks is inherently weaker due to the relatively high background levels for copper, palladium, and gold in the Nipigon diabase sills. However, the results of stream-water geochemistry over the Seagull and Disraeli ultramafic intrusions highlight their unique geochemical footprint on the surficial landscape, in particular with respect to Cr, Mg, and Ni, compared with the surrounding Nipigon diabase. In addition, lake sediments underlain by the Seagull, Disraeli, and Hele intrusions have distinctly elevated Cr concentrations and Gd/Yb ratios compared with the surrounding areas underlain by Nipigon diabase sills or Sibley Group rocks. Therefore, exploration value can be maximized over the Nipigon Embayment by exploiting these geochemical contrasts in surficial media to discriminate between ultramafic rocks and the surrounding Nipigon diabase sills. The results of this study highlight the importance of chromium concentrations in surficial media as a diagnostic feature for the presence of ultramafic rocks, regardless of their age or location. In general, a cost-effective exploration strategy for PGE mineralization includes targeting the associated metals (Cr, Ni) within drift deposits (C-horizon till) and drainage media (stream sediment, lake sediment) to vector to prospective mafic–ultramafic intrusive rocks, prior to detailed (property scale) follow-up, involving the determination of base metals and PGEs within soil, till, stream sediment, and peat samples. Relative to the metals copper, nickel, and chromium (ppm levels), the PGEs have significantly lower initial concentrations (ppb levels), are less mobile in the surficial environment, have significantly shorter glacial dispersion trains, and are less reliably determined at the laboratory.