Background: HER2 status is a predictive biomarker to response to trastuzumab in metastatic gastric adenocarcinomas. However, relatively little is known about the role of HER2 and HER3 in the non-metastatic disease in European population. Methods: Immunohistochemical expression of HER2 was analyzed using DAKO-HercepTest™ and gene amplification using DAKO-DuoCISH kit; both was scored according to published reports. HER3 expressión was analyzed using HER3 clon DAK-H3-ICHER3 and scored as follows: 0 = no staining, 1+ = light staining, 2+ = moderate staining, and 3+ = strong staining. Slides with score 0 or 1+ were classified as low expression or negative and slides with score 2-3+, as high expression or positive. According HER2 and HER3 status patients were classified into six subtypes: HER2-HER3 negative, HER2 equivocal expression HER3 negative, HER2 positive – HER3 negative, HER2 negative – HER3 positive, HER2 equivocal expression – HER3 positive and HER2-HER3 positive. The relationship between this classification and the clinicopathological characteristics and survival was analyzed retrospectively. Results: We included 106 patients between January 2007 and June 2014. The HER2 positivity was 13.2% and HER3 high expression was identified in 27.4% of patients. HER2 status was significantly associated with HER3 status (p = 0.018). HER2 equivocal or positive subtypes were associated with intestinal subtype (0.020) and HER2 or HER3 positive subtypes were associated with low histological grade (0.050). Our classification have demonstrated prognostic impact (p = 0.032) with a specific mortality rate due to gastric cancer of 45-50% for patients with equivocal or positive HER2 subtypes with HER3 low expression, 30% for patients with HER3 high expression independently of HER2 status, and 18% for patients HER2-HER3 negative. Conclusions: Our classification, using HER2 and HER3 status, stratifies patients into 6 subtypes with differentiated clinical and pathological characteristics and prognostic impact.