The differences and commonalities between x-ray fluorescence results obtained using synchrotron radiation and a portable x-ray fluorescence device were examined using arsenic in soft tissue phantoms and lead in bone phantoms. A monochromatic beam energy of 15.8 keV was used with the synchrotron, while the portable device employed a rhodium anode x-ray tube operated at 40 kV. Bone phantoms, dosed with varying quantities of lead, were made of Plaster of Paris and placed underneath skin phantoms of either 3.1 mm or 3.9 mm thickness. These skin phantoms were constructed from polyester resin, and dosed with varying amounts of arsenic. Using an irradiation time of 120 s, arsenic Kα and Kβ, and lead Lα and Lβ characteristic x-ray peaks were analysed. This information was used to calculate calibration line slopes and minimum detection limits for each data set. As expected, minimum detection limits were much lower at the synchrotron for detecting arsenic and lead. Both approaches produced lower detection limits for arsenic in soft tissue than for lead in bone when simultaneous detection was attempted. Although arsenic Kα and lead Lα emissions share similar energies, it was possible to detect both elements in isolation by using the arsenic Kβ and lead Lβ characteristic x-rays. Greater thickness of soft tissue phantom reduced the ability to detect the underlying lead. Experiments with synchrotron radiation could help guide future efforts toward optimizing a portable x-ray fluorescence in vivo measurement device.