There are many controversies regarding the treatment of very early-stage (pT1a/bN0M0) breast cancer (BC), generally considered to have a very good prognosis. The debate is the benefit of an adjuvant treatment of HER2-neu (namely HER-2)-positive subcentimetric carcinoma with trastuzumab. Current guidelines do not suggest, with the highest level of evidence, whether trastuzumab should be administered after adjuvant chemotherapy in the treatment of high-risk pT1a/bN0M0 breast cancer. The major phase III trials that confirmed the benefit of adjuvant immunotherapy did not include small (<1 cm diameter) node-negative breast cancer. Several retrospective case series of HER-2-positive pT1a/bN0M0 carcinoma seem to demonstrate that they have a higher risk of relapse compared to the HER-2-negative counterpart. HER-2 also seems to confer an independent risk of recurrence and/or death in a multivariate analysis within large node-negative breast cancer populations. In particular, the best way to select higher-risk tumours that may achieve the best results from a trastuzumab-based therapy appears to be the in situ hybridization, which should follow the new recommended algorithm of the ASCO/CAP guidelines in case of doubtful results. According to the evidence that the survival of HER-2-positive BC can be improved with the introduction of trastuzumab respect to the HER-2-negative counterpart, there is today less uncertainty about the curative role of anti-HER-2 therapy in very early disease.