In this fascinating discussion experts give their answers to the question ‘how can we understand myeloma at the single-cell level’. Specifically highlighted is the impact copy-number alterations of chromosome 1q have on outcomes, the interaction between the tumor cells and the tumor microenvironment, how this can predict treatment response and how single-cell analysis can identify signatures that drive resistance. Irene Ghobrial, MD of Dana-Farber Cancer Institute, Boston, MA, chairs this discussion with Rodger Tiedemann, PhD, ChB, MB of Princess Margaret Cancer Centre, Toronto, ON, Yael Cohen, MD of Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel and Eileen Boyle, MD, PhD, of NYU Langone, New York City, NY. This discussion took place at The International Workshop on Myeloma 2022, held in Scottsdale, AZ.