AIM: To analyze the characteristics of multiple primary malignancies (MPMs) of digestive system; including incidence, types of tumor combinations, time intervals between development of multiple tumors, clinical course,and prognostic factors affecting survival and mortality.METHODS: Data from a total of 129 patients treated from January 1991 to December 2000 for pathologically proved MPMs, including at least one originating from the digestive system, were reviewed retrospectively.RESULTS: Among 129 patients, 120 (93.02%) had two primary cancers and 9 (6.98%) had three primary cancers. The major sites of MPMs of the digestive system were large intestine, stomach, and liver. Associated nondigestive cancers included 40 cases of gynecological cancers, of which 31 were carcinoma of cervix and 10cases of genitourinary cancers, of which 5 were bladder cancers. Other cancers originated from the lung, breast,nasopharynx, larynx, thyroid, brain, muscle, and skin.Reproductive tract cancers, especially cervical, ovarian,bladder, and prostate cancers were the most commonly associated non-GI cancers, followed by cancer of the lung and breasts. Forty-three cases were synchronous, while the rest (86 cases) were metachronous cancers. Staging of MPMs and treatment regimes correlated with the prognosis between survival and non-survival groups.CONCLUSION: As advances in cancer therapy bring about a progressively larger percentage of long-term survivors, the proportion of patients with subsequent primary lesions will increase. Early diagnosis of these lesions, based on an awareness of the possibility of second and third cancers, and multidiscipiinary treatment strategies will substantially increase the survival of these patients.