Gemcitabine in combination with the oral epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib, is a treatment option for patients with advanced pancreatic cancer. Lung toxicity has been described for each of these drugs. A 59-year-old man with advanced non-small-cell lung cancer developed acute respiratory failure with bilateral interstitial lung disease 4 weeks after the onset of second-line combination therapy that included gemcitabine and erlotinib. Despite discontinuation of gemcitabine and erlotinib, treatment with corticosteroids was ineffective and the patient gradually deteriorated and died with progressive respiratory failure 2 months after the start of the gemcitabine/erlotinib combination. It was concluded that a synergistic effect between gemcitabine and erlotinib could have been responsible for this fatal pulmonary toxicity. Physicians should be aware of the potential severe lung toxicity of this combination. The potential role of corticosteroids in the management of this toxicity is unknown.