Like protein-coding genes, loci that produce microRNAs (miRNAs) are generally considered to be under purifying selection [1-3], consistent with miRNA polymorphisms being able to cause disease . Nevertheless, it has been hypothesized that variation in miRNA genes may contribute to phenotypic diversity [1, 3, 5, 6]. Here we demonstrate that a naturally occurring polymorphism in the MIR164A gene affects leaf shape and shoot architecture in Arabidopsis thaliana, with the effects being modified by additional loci in the genome. A single base pair substitution in the miRNA complementary sequence alters the predicted stability of the miRNA:miRNA* duplex. It thereby greatly reduces miRNA accumulation, probably because it interferes with precursor processing. We demonstrate that this is not a rare exception and that natural strains of Arabidopsis thaliana harbor dozens of similar polymorphisms that affect processing of a wide range of miRNA precursors. Our results suggest that natural variation in miRNA biogenesis resulting from cis mutations is a common contributor to phenotypic variation in plants.