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 were scored according to published criteria. HER3 expressión was analyzed using HER3 clon DAK-H3-ICHER3 HER2 patients with 0-1+ were classified as HER2 negative, patients with 2+ and negative DuoCISH as equivocal and 3+ or 2+ with positive DuoCISH as positive. HER3 pts were classified as negative if 0-1+ or positive 2-3+ by two independent observers. Six subtypes according to HER2 and HER3 status were defined. Relationship between this classification and the clinicopathological characteristics and survival was analyzed retrospectively. Results: 106 pts diagnosed between Jan-2007 and Jun-2014 were analyzed. Subtype distribution was: HER2-HER3 (-) (56.6%), HER2 equivocal/HER3 (–) 9 pts (8.5%), HER2 (-) HER3 (+) (15.1%), HER2 equivocal HER3 (+) (6.6%), HER2 (+) HER3 (-) (7.5%) and HER2 (+) HER3 (+) (5.7%). HER2 had a significant association with HER3 (p = 0.018). Strong or moderate HER2 expression was associated with intestinal differentiation (p = 0.020) while tumors with strong or moderate HER2 expression or high HER3 expression were associated with lower grade (p = 0.050). Patients with low expression of HER2 and HER3 had a better specific overall survival ( > 85%) than those with HER3 overexpression (66.7-68.6%). Patients with strong or moderate HER2 expression without HER3 expression tumors had the worse survival (50%). Conclusions: Our algorithm based in HER2 and HER3 status proposes a classification in 6 groups with clinicopathologic and prognostic correlates. Overexpression of HER3 is a frequent phenomenon in early gastric cancer that modulates the adverse prognosis associated with HER2 overexpression. Patients with HER3 overexpression have an intermediate prognosis between patients with isolated HER2 overexpression and those who lack both drivers.