BACKGROUND There are gender differences in multiple primary malignancies associated with lung cancer (MPMLC) in terms of clinical characteristics. However, the importance of these differences in the management of patients has not been clarified. OBJECTIVE Differences in characteristics affected by gender were investigated in MPMLC to identify factors important for the proper management of the patients. METHODS Univariate and multivariate analyses were performed between 82 male and 34 female patients with MPMLC treated from August 1982 to March 2002. RESULTS In univariate analysis, the numbers of smokers or ex-smokers, smoking-related cancer and synchronous multiple primary malignancies were significantly increased in males with MPMLC (p < 0.0001, p < 0.05 and p < 0.05, respectively). In multivariate analysis, synchronous multiple primary malignancies and the number of smokers or ex-smokers were significantly different between male and female MPMLC. Gastric, lung and colon cancers were major constituents in male MPMLC, and 40.2% of all malignancies were smoking-related cancers. On the other hand, breast and uterine cancers were major constituents in female MPMLC, and only 20.6% of all MPMLC were smoking-related cancers. CONCLUSIONS Male patients with MPMLC demonstrated significant smoking history and synchronous multiple primary malignancies, indicating the need for different approaches to properly manage and follow up male versus female MPMLC patients.