Purpose: To evaluate the class 2 gene expression profiling of patients with small and medium-small uveal melanoma, focusing on tumor control, metastases, and mortality. Methods: This retrospective case series evaluated patients treated for small or medium-small uveal melanoma by the same surgeon. Patients with small uveal melanoma were treated with microincision vitrectomy surgery or brachytherapy, and patients with medium-small uveal melanoma were treated with brachytherapy. All patients were gene expression profiling class 2. Results: Forty-two patients (21 with a diagnosis of small melanoma; 21 with a diagnosis of medium-small melanoma) with a mean age of 58 years and a confirmed diagnosis of class 2 gene expression profiling melanoma were identified. The melanoma-specific mortality at the 5-year follow-up was 4.8% (1/21) for patients with small melanoma and 14.3% (3/21) for patients with medium-small melanoma. The rate of melanoma-specific active metastasis at 5 years was 4.8% (1/21) for patients with small melanoma and 14.3% (3/21) for patients with medium-small melanoma. In both groups, the enucleation rate at 5 years was 0%. Conclusions: Small tumor management achieves excellent anatomic and visual outcomes but mandates diagnostic accuracy and defined long-term outcomes as well as follow-up (5-year minimum in this series). Gene expression profiling classification is important in prognostication; however, early treatment of small tumors significantly decreases the predicted mortality and has the greatest potential effect on patient survival, even for class 2 melanomas.