Tumor necrosis factor (TNF)-alpha inhibitors have been used effectively to treat rheumatoid arthritis and inflammatory bowel disease. Although the role of TNF-alpha in tumor development is not well understood, an increased risk of malignancies with anti-TNF-alpha therapy has been suggested. We report an instructive case of a patient, treated for Crohn's disease with infliximab, who presented with a neck abscess diagnosed to be head and neck squamous cell carcinoma. The patient's clinical course illustrates a temporal relationship between reappearance of his cancer after a complete response to therapy and the resumption of infliximab for worsening Crohn's disease.