Fragile quantum effects such as single electron charging in quantum dots or macroscopic coherent tunneling in superconducting junctions are the basis of modern quantum technologies. These phenomena can only be observed in devices where the characteristic spacing between energy levels exceeds the thermal energy, k B T , demanding effective refrigeration techniques for nanoscale electronic devices. Commercially available dilution refrigerators have enabled typical electron temperatures in the 10 . . . 100 mK regime, however indirect cooling of nanodevices becomes inefficient due to stray radiofrequency heating and weak thermal coupling of electrons to the device substrate. Here we report on passing the millikelvin barrier for a nanoelectronic device. Using a combination of on-chip and off-chip nuclear refrigeration, we reach an ultimate electron temperature of T e = 421 ± 35 µK measured by a Coulomb-blockade thermometer. With a hold time exceeding 85 hours below 700 µK, we provide a landmark demonstration of nanoelectronics in the microkelvin regime.Accessing the microkelvin regime [1] holds the potential of enabling the observation of novel electronic states, such as topological ordering [2], electron-nuclear ferromagnets [3,4], p-wave superconductivity [5] or non-Abelian anyons [6] in the fractional quantum Hall regime [7]. In addition, the error rate of various quantum devices, including single electron charge pumps [8] and superconducting quantum circuits [9] could improve by more effective thermalization of the charge carriers.The conventional means of cooling nanoelectronic devices relies on the thermal coupling between the refrigerator and the conduction electrons, mediated by phononphonon coupling in the insulating substrate,Q p-p ∝ T 4 p1 − T 4 p2 and electron-phonon coupling in the devicė Q e-p ∝ T 5 e − T 5 p [10, 11], both rapidly diminishing at low temperatures. In a typical dilution refrigerator, T p > 5 mK, and specially built systems reach 1.8 mK [12], which limits T e > T p to the millikelvin regime. The lowest static electron temperature reached with this technique was T e = 3.9 mK [13] in an all-metallic nanostructure, and other experiments reached similar values [14][15][16] in semiconductor heterostructures.This technological limitation can be bypassed by adia- * These authors contributed equally to this work.batic magnetic refrigeration, which relies on the constant occupation probability of the energy levels of a spin system, ∼ exp(−gµBm/k B T ) in the absence of heat exchange with the environment [17]. Here, k B T is the thermal energy at a temperature of T , gµB is the energy split between adjacent levels at a magnetic field of B and m is the spin index. Thus, the constant ratio B/T allows for controlling the temperature of the spin system by changing the magnetic field. Exploiting the spin of the nuclei [18,19], this technique has been utilized to cool bulk metals down to the temperature range of T ∼ 100 pK [20]. If only Zeeman splitting is present, which is linear in B, the ultimate tempe...