Trastuzumab is known for its clinical activity in women with HER2-overexpressing breast cancer. Randomized clinical trials have shown significant improvement in disease-free and overall survival with trastuzumab administered in conjunction with adjuvant chemotherapy for early-stage HER2-positive breast cancer. However, there is no direct evidence of clinical benefit from adjuvant trastuzumab in patients with node-negative, HER2-overexpressing, small (T1a-b) breast cancers. Previous literature shows that most breast cancers with node-negative small tumors have a good prognosis, but HER2-overexpressing disease might still be worse in this population. Some recent retrospective studies showed that an adjuvant trastuzumab-based regimen has a better prognostic effect, even in patients with node-negative, HER2-overexpressing, small breast cancers, although absolute survival differences were small. On the basis of the available literature, we believe that trastuzumab should be considered for patients with minimal HER2-overexpressing disease, although tools for accurate selection of patients at risk of relapse still need to be developed.