This book constitutes the refereed proceedings of the 12th International Conference on Software Business, ICSOB 2021, which was held during December 2-3, 2021. The conference was originally planned to take place in Drammen, Norway, but changed to an online format due to the COVID-19 pandemic. The special theme of ICSOB 2021 was software sustainability. The 13 full papers and 5 short papers presented were carefully reviewed and selected from 39 submissions. They deal with a range of topics including software sustainability, Agile development, DevOps, software startups, prototyping, software ecosystems, crowdsourcing platforms, technical debts, and risk management.