Multiple primary gastric adenocarcinomas (MPGA) have been reported from 3.5% to 10% of the patients. The presence of MPGA in the same stomach at the time of resection may alter the extension of surgical treatment. Moreover, the route of carcinogenesis has not been clearly clarified in these tumors (mutator pathway or suppressor pathway). Aim: to evaluate clinicopathologic and immunohistochemical characteristics of MPGA. Methods: Hospital records from 1995 to 2003 of the gastric cancer patients regarding the presence of MPGA were retrospective reviewed, and compared to the patients who had solitary adenocarcinomas in the same period. Immunohistochemistry for p53 (suppressor pathway) and for hMLH1, hMSH2 and hMSH6 (mutator pathway) was performed using streptavidin-biotin complex method. Results: 553 patients underwent gastric resection during the studied period. MPGA was detected in 19 (3.43%) of the patients. Thirteen (68.4%) were men and the mean age was 64.8 (range = 15-81 years-old). Sixteen patients had two separated tumors and three patients had three tumors. The tumors were localized in distal stomach in 22; body in 14 and proximal in 5. In fourteen patients the lesions were close to each other (less than 3 cm), while in five patients the neoplasias were distant, in another portion of the stomach. There was no statistical difference between age, gender and tumor location when a comparison with the solitary lesions was performed. There was a predominance of intestinal type tumors in the group of synchronic tumors compared to the solitary lesions, 73.2% vs. 38.5%, p=0.016. Moreover, synchronic neoplasias were diagnosed in earlier stage than solitary neoplasias, T1-T2 = 47.4% vs. T1-T2 = 25.9%, p=0.01; and N0-N1 = 73.7%, vs. N0-N1 = 55.2%, p=0.001. Immunohistochemistry for p53 was detected in 58.5% of the MPGA. Altered hMLH1 immunoexpression occurred in 19% patients and hMSH6 in 4.8%. Immunostaining for hMSH2 was positive in all MPGA, indicating absence of alterations of this repair gene marker. There was an inverse association between immunoexpression of hMLH1 and p53 in MPGA. Thus, p53 was solely detected in 17 tumors, while hMLH1 was altered in 14/24 negative p53 tumors, p=0.01. Conclusions: 1. MPGA presented higher frequency of intestinal type and early gastric cancer in comparison to solitary gastric cancer; 2. Two routes of carcinogenesis, mutator and suppressor, appears to be involved independently in the development of MPGA; 3. Carefull endoscopic examination of the entire stomach should be performed in patients with gastric cancer to avoid missed lesions.