A new portable x-ray fluorescence (XRF) screening tool was evaluated for its effectiveness in arsenic (As) quantification in human finger and toe nails ([Formula: see text]). Nail samples were measured for total As concentration by XRF and inductively coupled plasma-mass spectrometry (ICP-MS). Using concordance correlation coefficient (CCC), kappa, diagnostic sensitivity (Sn) and specificity (Sp), and linear regression analyses, the concentration of As measured by XRF was compared to ICP-MS. The CCC peaked for scaled values of fingernail samples, at 0.424 (95% CI: 0.065-0.784). The largest kappa value, 0.400 (95% CI: -0.282-1.000), was found at a 1.3 μg g(-1) cut-off concentration, for fingernails only, and the largest kappa at a clinically relevant cut-off concentration of 1.0 μg g(-1) was 0.237 (95% CI: -0.068-0.543), again in fingernails. Analyses generally showed excellent XRF Sn (up to 100%, 95% CI: 48-100%), but low Sp (up to 30% for the same analysis, 95% CI: 14-50%). Portable XRF shows some potential for use as a screening tool with fingernail samples. The difference between XRF and ICP-MS measurements decreased as sample mass increased to 30 mg. While this novel method of As detection in nails has shown relatively high agreement in some scenarios, this portable XRF is not currently considered suitable as a substitute for ICP-MS.