Desmoplastic fibroma (DF) is a rare bone tumor that accounts for about 0.1%-0.3% of all bone tumors. It is typically characterized as slow growing, but in rare cases it can proliferate extensively and exhibit locally aggressive characteristics. It is found most commonly in the appendicular skeleton and rarely in the axial skeleton. The authors present the cases of 2 women in their 20s with DF originating from the cervicothoracic spine. Both tumors intimately involved the brachial plexus and caused significant impingement of the mediastinum resulting in cardiopulmonary compromise. Both patients underwent hemiclamshell thoracotomies for tumor resection, and in both cases subtotal resection was performed given the encasement of the brachial plexus. Although DF is a benign process, it can be locally aggressive and proliferate at extensive rates. The authors describe these 2 cases, review the literature, and discuss management.