Oxaliplatin in combination with 5-fluorouracil (5-FU) and Leucovorin (FOLFOX) currently represents a valid approach for treating advanced colorectal cancer. In Japan, it is generally performed. Gastrointestinal, hematological and neurosensory toxicities are the most common. However, information concerning the pulmonary toxicity of this regimen is very limited. We report here two cases of interstitial lung disease occurring in association with the use of this combination chemotherapy. Reports of interstitial lung disease due to FOLFOX are infrequent, but could lead to severe complications. It is important to perform an X-ray examination regularly and detect symptoms early.