A 36-year-old woman with no medical or surgical history was evaluated for weight loss. Abdominal computed tomography (CT) showed signs of Crohn's disease, which was later confirmed endoscopically. She was started on tumor necrosis factor-α (TNF-α) inhibitor therapy. Nine months after treatment, she experienced additional weight loss and a 7 x 8 x 8-cm mass on repeat CT. Biopsy revealed retroperitoneal fibromatosis, so TNF-α was continued. Repeat CT showed an enlarged mass. TNF-α therapy had a suspected role in mass growth, therapy was discontinued, and the mass surgically resected. One year after resection, she has regained weight with no recurrence of the mesenteric fibromatosis.