Locally advanced, nonresectable, radioresistant tumors can often be ablated by external irradiation using high-energy fast neutron beams. Long-term local control has been achieved in a wide range of malignant tumors, notably sarcomas of bone and soft tissue and adenocarcinomas in various sites. Complete response and long-term remission, with local control rates between 50% and 70%, have been reported in a number of very large osteogenic sarcomas, soft-tissue sarcomas (particularly neurogenic tumors), melanomas, and adenocarcinomas of the alimentary tract. Malignant salivary gland tumors and carcinoma of the prostate appear to be the most responsive to neutrons, with a high frequency (70% to 90%) of successful remission and significantly improved survival even in advanced stages of disease. The biological mechanisms underlying radioresistance of tumor cells and the rationale for using heavily ionizing particles are described. Neutrons are shown to be a valuable adjunct in managing nonresectable malignant tumors that resist conventional therapy.