Seroma formation following posterior cervical laminectomy and fusion is now recognized as a rare but significant risk. Previous reports have attributed the development of postoperative seromas to the use of recombinant bone morphogenetic protein-2 (rhBMP-2). Here the authors present the case of a 78-year-old female with a history of osteoporosis who developed delayed postoperative neck and shoulder pain following posterior cervical laminectomy and fusion utilizing only autograft bone and demineralized bone matrix (DBM) allograft. Postoperative MRI demonstrated normal hardware placement and a large epidural fluid collection that extended from C-4 to C-6. The patient underwent decompression and drainage of her sterile postoperative seroma. To the authors' knowledge, no case of seroma formation with the use of DBM has been previously reported. This case suggests that although rhBMP-2 is involved in the majority of postoperative seroma developments, other osteoinductive agents such as DBM can contribute to the development of a symptomatic seroma. This report presents an illustrative case study and reviews the current understanding of the development of and treatment for cervical seroma following posterior cervical laminectomy and fusion.