Numerous small nucleolar RNAs (snoRNAs) appear to be required for 2'-O-ribose methylations of eukaryotic ribosomal RNA. Most of the genes for this snoRNA family had been unidentified, despite the availability of a complete Saccharomyces cerevisiae genome sequence. Using new probabilistic modeling methods akin to methods used in speech recognition and computational linguistics, we computationally screen the yeast genome and identify 22 new methylation guide snoRNAs, snR50-snR71. Gene disruptions and other experimental characterization of these and other previously proposed guide snoRNAs confirm their methylation guide function. In total, we assign 51 of the 55 ribose methylated sites in yeast rRNA to 41 different guide snoRNAs.