Metals continue to impose health issues among world populations. A non-invasive alternative biomarker for assessment of metals and other elements has been explored in other studies using toenail samples. Some benefits of using toenails as biomarkers over blood samples include cost efficiency, ease of collection, and a longer biological half-life within samples. The objective of this study was to employ desktop XRF for the purpose of measuring metal concentrations in human nail samples, thus conducting a non-destructive assessment. These benefits paired with comparable accuracy in exposure detection could prove toenail samples to be a preferred biomarker for many studies. Current elemental quantification techniques in toenail samples could be improved. The standard practice for measuring metal exposure in toenails, inductively coupled plasma mass spectrometry (ICP-MS), has a counterpart in x-ray fluorescence. While maintaining similar quantification capabilities, x-ray fluorescence could provide decreased cost, preservation of samples, and ease of operation. Portable XRF machines have been tested for measuring toenail samples, but they have drastically increased detection limits in comparison to ICP-MS. New benchtop XRF systems should give comparable detection limits to ICP-MS. This study compares the benchtop XRF measurements of lead (Pb), copper (Cu), iron (Fe), and Selenium (Se) levels to that of ICP-MS measurements of toenail samples and calculates estimated detection limits for 23 other elements. We found strong correlations for the toenail lead (R² = 0.92), copper (R² = 0.95), selenium (R² = 0.60), and iron (R² = 0.77) comparison between desktop XRF and ICP-MS measurements. Median minimum detection limits over the 23 elements were found to be 0.2 μg/g using a 7.5-min measurement. Benchtop XRF provides a lower detection limit than previously studied portable XRF machines, which gives it the capability of accurately detecting almost any desired element in nail samples. Benchtop XRF provides a non-destructive alternative to ICP-MS in surveillance of nail samples.