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In general, each codon specifies a single amino acid, but some can specify a different amino acid, depending on where they are in the mRNA. For example, the codons AUG and GUG encode formylmethionine if they are at the beginning of the coding region but encode methionine or valine, respectively, if they are internal to the coding region. The codons CUG, UUG, and even AUU also sometimes encode formylmethionine if they are at the beginning of a coding sequence.

The codon UGA is another exception. This codon is usually used for termination but encodes the amino acid selenocysteine in a few positions in genes (Box 2.5) and encodes tryptophan in some types of bacteria. Similarly, UAG is usually used for termination but can be used to encode the novel amino acid pyrrolysine in certain organisms.