Aim: Metal carbenic complexes have received considerable attention in both the catalysis and biological fields for their potential applications in cancer and antimicrobial therapies. Results: A small series of new silver and gold N-heterocyclic carbene complexes has been designed and synthesized. Among the tested complexes, one compound was particularly active in inhibiting anchorage-dependent and -independent breast cancer proliferation, and inducing cell apoptosis via a mitochondria-related process. The antitumor activity was associated to the transcriptional activation of the tumor suppressor gene p53 in an Sp1-dependent manner, as evidenced by biological and docking studies. Conclusion: Our results highlight the importance and the versatility of N-heterocyclic carbene complexes of gold and silver as useful tools against breast cancer progression.