This study aims to investigate the potential of portable X-ray fluorescence spectrometry (pXRF) for identifying pathological conditions in archaeological human skeletal remains. Bone element distribution in relation to known disease categories is analyzed using pXRF from the femora of 73 individuals (34 adult; 39 non-adult) from the post-Medieval Coach Lane skeletal collection (Durham University). There were no significant differences in the elemental ratios of individuals with scurvy, rickets, and cribra orbitalia. Potential alterations in elemental content were observed in relation to syphilis (Mn/S, Mn/Cl, and Ba/Cl) and neoplastic disease (Ba/Sr, S/Sr, Mn/Fe, and Zn/Cl). It is likely that post-depositional diagenetic changes, potentially exacerbated by the industrial location of the burial site, altered the elemental content of the individuals sampled and thereby effectively obscured any pathological changes detectable by pXRF.