Potentiometric sensors based on silicon nanowire field effect transistors (SiNW FETs) typically display exquisite sensitivities, but their bioanalytical implementation is limited due to the need for stringent measurement conditions and high-precision readout units. An alternative operation principle where SiNW FETs are operated in a frequency-domain electrical impedimetric approach is promising. However, to date only limited data is available in regard to the sensing performance and translational relevance of this novel approach in comparison to the standard charge detection paradigm. We demonstrate the feasibility of conducting electrical impedimetric FET measurements with a portable unit for the ultrasensitive detection of cancer biomarkers in biospecimens. Compared to standard potentiometric measurements, electrical impedimetric FET measurements yielded significant improvements in biosensing performances, including the limit of detection, sensing resolution, and dynamic range.