AbstractThe possibility that neutrinos may be their own antiparticles, unique among the known fundamental particles, arises from the symmetric theory of fermions proposed by Ettore Majorana in 1937¹. Given the profound consequences of such Majorana neutrinos, among which is a potential explanation for the matter–antimatter asymmetry of the universe via leptogenesis², the Majorana nature of neutrinos commands intense experimental scrutiny globally; one of the primary experimental probes is neutrinoless double beta (0νββ) decay. Here we show results from the search for 0νββ decay of ¹³⁰Te, using the latest advanced cryogenic calorimeters with the CUORE experiment³. CUORE, operating just 10 millikelvin above absolute zero, has pushed the state of the art on three frontiers: the sheer mass held at such ultralow temperatures, operational longevity, and the low levels of ionizing radiation emanating from the cryogenic infrastructure. We find no evidence for 0νββ decay and set a lower bound of the process half-life as 2.2 × 10²⁵ years at a 90 per cent credibility interval. We discuss potential applications of the advances made with CUORE to other fields such as direct dark matter, neutrino and nuclear physics searches and large-scale quantum computing, which can benefit from sustained operation of large payloads in a low-radioactivity, ultralow-temperature cryogenic environment.