Objective: To report a novel case of Tarceva^? treatment for small cell lung carcinoma resulting in tympanic membrane necrosis. Patient: A 49-year-old male with tympanic membrane necrosis and presumed resistant acute otitis externa and chronic inflammation of the left ear. Patient is status post chemotherapy and radiation diagnosed with non-small cell lung cancer in December 2008 with on-going therapy with Tarceva^? for residual disease. Intervention: Tympanoplasty of left ear. Results: Improvement of symptoms of irritation and improvement of hearing and speech reception thresholds. All acid fast bacilli, fungal and bacterial cultures of the intra-op specimen were negative. Conclusions: The possibility that long term Tarceva^? therapy could have caused the tympanic membrane necrosis and acute otitis media like symptoms is feasible since Tarceva^? is an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase. Upon activation of EGFRs it undergoes a transition from inactive monomeric form to active homodimer or hertodimer with another member of the ErbB receptor family. This then initiates several signal transduction cascades, leading to DNA synthesis and cell proliferation. Activation of the receptor is important in the innate immune response in human skin. Some of the common side effects include an aceiform skin rash but this is the first reported link between tympanic membrane necrosis and Tarceva^?.