Background: Circulating tumor cells (CTCs), a potential biomarker for cancer diagnosis and treatment monitoring, are characterized by high heterogeneity and scarcity in peripheral blood, making them difficult to be detected by conventional laboratory methods. In this context, the use of alternative methods such as dielectrophoresis and broadband dielectric spectroscopy as complementary tools for CTCs detection is of great interest. One first methodological issue related to the abovementioned techniques is related to choosing the optimal buffer solution, as the buffer can have a negative impact on CTCs fragility and electrode polarization. Thus, the aim of this study is to determine the optimal buffer solution when measuring the dielectric parameters of CTCs.Materials and method: Three commonly used sucrose-base buffers were tested. The dielectric measurements were conducted using the Novocontrol Alpha A Analyzer and the BDS 1200 sample measuring cell. We determine the dielectric properties of the solutions without and with suspended THP-1 cells. Subsequently, equivalent Randles electrical circuits were designed.Results: An impedance decrease of at least 40% over the frequency range from 10 Hz to 5000 Hz and a significant increase of the phase angle for the 200Hz domain were observed in sucrose + HEPES solution when THP-1 cells were added, while no changes were encountered in the other buffers.Conclusion: Sucrose + HEPES solution was the most suitable buffer for this kind of experiment. The article highlights the importance of choosing the appropriate buffer for dielectric measurements of CTCs, demonstrating the method’s feasibility for clinical use.