A year ago, the first edition of the Tumor Heterogeneity, Plasticity and Therapy conference, was planned in Leuven. As the global pandemic intervened, the conference was postponed to 2021 and switched to a virtual format. While a completely online conference comes with its challenges, this first edition was definitely a success. The impressive line-up of speakers and the diverse program attracted 420 attendees, who contributed to the interactive atmosphere together with speakers, sponsors and organizers.