Provided herein are buffers for the stabilization of nucleic acid molecules. The buffers find particular use for the stabilization of trace amounts of nucleic acid molecules in a variety of environments, including repeated freeze/thaw cycles. For example, in some embodiments, provided herein are compositions comprising tris(hydroxymethyl)aminomethane (Tris), ethylenediaminetetraacetic acid (EDTA), polyadenylic acid, and a synthetic DNA oligonucleotide.