Recent RNA-sequencing (RNA-seq) analyses in various malignancies, including CLL [15] and breast cancer [16], uveal melanoma [16,17,18] and MDS [19,20,21], indicate that the most common mutations of SF3B1 lead to a global splicing defect characterized by the production of aberrant transcripts through the use of cryptic 3’ splice sites and alternative branch points. The gene discussed is SF3B1; the disease is uveal melanoma.