Synchronous bronchiolo-alveolar cell carcinoma (BAC) in both lungs and squamous cell carcinoma in left lung were found in a 66-year-old male smoker. After two courses of chemotherapy with gemcitabine and carboplatin, the left lung mass had partially resolved, however, the extent of BAC had been increased. When gefitinib was used as a second-line chemotherapy, the consolidation lesions of BAC was improved while the mass of squamous cell carcinoma was aggravated. The analysis of epidermal growth factor receptor-tyrosine kinase (EGFR-TK) mutations showed that BAC had the deletion, delE746-A750 in exon 19, however, squamous cell carcinoma had no mutations. These synchronous tumors with different location, histology, status of EGFR-TK mutations and response to chemotherapy might be caused by different molecular pathogenesis.