<title>Author Summary</title> <p>Given fixed resources, plants have a choice whether to produce many small seeds or a few large seeds. In terms of reproductive fitness, there are costs and benefits to both strategies. As a result, plant species vary more than 100,000-fold in both seed size and seed output. The current study focuses on understanding the molecular and developmental basis of a single genetic locus (or quantitative trait locus) that determines seed size between the cultivated tomato and its wild relatives. We show that the cause of size variation can be traced to a gene encoding an ABC transporter protein. The gene apparently exercises its control on seed size through expression in the developing seeds and not the mother plant that nurtures those seeds. A comparison with the model plant <italic>Arabidopsis thaliana</italic> suggests that the ABC transporter identified in tomato may also control seed size in other plants, opening research opportunities for understanding plant adaptation and for potentially modulating seed size in crop plants for human purposes.</p>