This book constitutes the refereed proceedings of the Third International Symposium on Mathematical and Computational Oncology, ISMCO 2021, held in October 2021. Due to COVID-19 pandemic the conference was held virtually. The 3 full papers and 4 short papers presented were carefully reviewed and selected from 20 submissions. The papers are organized in topical sections named: statistical and machine learning methods for cancer research; mathematical modeling for cancer research; spatio-temporal tumor modeling and simulation; general cancer computational biology; mathematical modeling for cancer research; computational methods for anticancer drug development.