In recent years, experimental tests related to building components through laboratory facilities have relatively matured. The techniques are based on one-dimensional heat transfer by creating a permanent temperature difference over a specimen to control heat fluxes. The three main methods are the Guarded Hot Box (GHB) method, the Calibrated Hot Box (CHB) method, and the Heat-Flow Meter method (HFM). The HFM method is the most widely applied technique for measuring on-site U-values of building components and several scientific works stressed the need for high temperature differences between the environments, suggesting 10 °C or 15 °C. However, temperature stability and high temperature gradients are difficult to obtain, especially for Mediterranean climatic conditions. Starting from this, an experimental study was conducted through a GHB apparatus, setting temperature differences from 2 °C to 20 °C between the hot and cold chambers. Heat flow measurements were performed to compute the thermal conductance of a specimen characterized by a known stratigraphy, thus highlighting the effect of the low thermal gradient on data acquired by the heat flow sensor. It was found that, even for low temperature differences (2 °C) maintained by ensuring stable thermal conditions, the experimental results are comparable with those obtained for higher and usual temperature differences (20 °C).