Many-grained mutants occurring spontaneously among their less well-endowed field mates may have appeared to early farmers as fortunate twists of fate foreboding wealth and abundance. In domesticated barley, the number of kernel rows in spike can be tripled by recessive mutant alleles at the Six-rowed spike 1 (vrs1) locus that abolish the suppression of lateral spikelet fertility. In another barley row-type, so called intermedium-spike (int), lateral floret size is often intermediate between six-and two-rowed types. Phenotypic and sequence analyses of our intermedium-spike collection revealed that other genes can increase the size of florets and even stimulate occasional grain setting in lateral spikelets. Here, we show that a complete six-rowed phenotype occurs in a diverse panel of intermedium-spike barley carrying wildtype Vrs1 in the presence of the Int-c.a allele of the intermedium spike-c (int-c) gene, previously considered only as a modifier of lateral spikelet fertility. Int-c.a-type alleles had arisen before domestication and are associated with the enlargement of lateral florets in wild barley, suggesting that natural selection/evolution acts towards reduced lateral floret size. Since Int-c.a cannot overcome the suppression of lateral florets in the genomic background of wild barleys, we infer the existence of other gene loci, at which novel alleles or allelic combinations were selected for after domestication, to increase grain number of barley independently of Vrs1.