Aggressive fibromatosis (desmoid tumor) of the neck is rare. When feasible, surgery is the best treatment option. However, complete excision with negative margins is not possible in most cases because of the involvement of vascular and nervous structures. Also, surgery results in poor functional and aesthetic outcomes. Sometimes debulking surgery with positive margins is performed, but the anatomy of the neck is a challenge for oncologic surgeons, and recurrences are not uncommon. Radiotherapy is seldom employed for the same reasons. On the other hand, systemic treatment with chemotherapy, hormone therapy, and noncytotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) has been used with good results. We report a case of inoperable aggressive fibromatosis of the neck that was successfully treated for about 21 months with a combination of chemotherapy and the NSAID indomethacin. As far as we know, this is the first reported use of a combination of chemotherapy and an anti-inflammatory drug in the treatment of aggressive fibromatosis of the neck. We also review the literature on cases of aggressive fibromatosis of the neck that have been reported over the past 12 years.